CT引导下经皮微波消融作为进展期非小细胞肺癌的维持治疗新手段

发布时间：2018-02-09 11:46

本文关键词： 非小细胞肺癌 CT引导下经皮微波消融无进展生存时间总生存时间　出处：《山东大学》2016年博士论文　论文类型：学位论文

【摘要】：目的：肺癌是世界范围内癌症的主要死因,中国是世界第一肺癌大国,肺癌居我国癌症发病率和死亡率的首位。非小细胞肺癌占全部肺癌病例的89%。进展期非小细胞肺癌失去了根治性手术的机会,目前以系统化疗为主要治疗手段。然而,传统一线治疗已经达到了疗效平台,总缓解率25%-35%,疾病进展时间3-5月,中位生存时间8-10月,1年生存率30-40%,2年生存率10-15%。大多数患者在一线治疗期间就出现了进展,即使是经一线治疗达到缓解或稳定的患者,最终也不可避免地出现进展,因此,总体上患者预后极差。对于经一线治疗达到缓解或稳定的患者,采用非铂类细胞毒药物或靶向药物维持治疗可以延迟进展。然而,维持治疗的应用受到一线治疗药物毒性和体力状况的限制,长期维持治疗患者耐受性差；维持治疗的疗效受到一线治疗疗效、组织病理类型、基因突变(融合)情况的影响；尽管有研究证实维持治疗能够延长无进展生存时间,但没有强烈证据证实其能够显著延长总生存时间；维持治疗的疗效并不优于在疾病进展后才开始的二线治疗。能量消融是采用热或非热方式直接消灭局部肿瘤的治疗方式。其中,微波消融是采用频率范围在300 MHz-300 GHz之间的电磁波对肿瘤细胞产生高温热损伤从而诱导其凝固性改变的治疗方式。影像引导下经皮微波消融是一种新兴的安全、有效的肺癌微创治疗手段,可以降低肿瘤的局部复发风险,且其疗效不受组织病理类型和基因突变(融合)情况影响。因此,或可用于经一线治疗达到部分缓解或稳定的患者,进一步消灭残留肿瘤细胞、减少局部复发,最终达到延长生存时间、改善生活质量的目的。本研究旨在评价CT引导下经皮微波消融作为经一线治疗后达到部分缓解或稳定的进展期非小细胞肺癌患者的维持治疗新手段的安全性和有效性,并探索相关预后因素。材料和方法：纳入2010年1月——2014年3月之间获得病理学确诊的全部IIIB期和IV期非小细胞肺癌患者,其中包括部分早期根治性手术后复发和(或)转移再分期为进展期的病例。所有患者接受标准一线治疗：化疗方案为含铂两药标准方案,每21天重复为一周期,共4-6周期；具有表皮生长因子受体敏感突变的患者接受靶向治疗；IIIB期患者接受同步放化疗序贯化疗。一线治疗后采用《实体瘤疗效评价标准》1.1版评价疗效。针对其中达到部分缓解或稳定的患者由多学科评估后接受微波消融治疗。经皮微波消融操作全程在CT引导下进行,麻醉采用局麻联合超前镇痛方式,严格执行无菌操作技术规范。为了使各消融区域重叠以形成足够大或适形的消融区域,根据肿瘤大小的不同主要有三种消融模式：①直径≤3 cm的小肿瘤采用单针单点模式；②直径3-5 cm的中等大小肿瘤采用单针多点模式；③直径5 cm的大肿瘤应采用多针多点模式。将微波天线穿刺达靶肿瘤底部,并根据消融过程中CT图像的变化适当调整微波天线的位置和深度,直至靶肿瘤完全被消融区域覆盖且围绕以5-10mm宽的安全边缘或达到预设的影像学终点为止。消融完毕后,要先消融针道后方可拔除微波天线以免针道出血、肿瘤种植。以消融后1月的增强CT作为新的基线资料,以后每3月复查增强CT,采用《影像引导下肿瘤消融的术语规范和报告标准》评价消融疗效。并发症采用《常见不良反应事件评价标准》4.03版报告。结果：一线治疗后,19例(54.3%)疗效评价为部分缓解,16例疗效评价为稳定。针对此35例患者的39个肿瘤进行了39次微波消融。其中,3次消融同时治疗2个肿瘤,3例患者的3个肿瘤进行了2次消融。全部39次消融均按规范进行操作,技术成功率达100%。26次消融使用单根微波天线操作,13次消融使用两根微波天线操作。中位消融功率为70 W(范围60-75 W),中位消融持续时间为7分钟(范围3-15分钟)。达最佳总疗效至首次消融的中位时间间隔为1月(范围7天-22月)。局部疗效：首次消融后1月,32个肿瘤(82.1%)达到完全消融,7个肿瘤(17.9%)为不完全消融。其中1个不完全消融的肿瘤经过再次消融后达到了完全消融；另2个姑息止痛效果不佳的肿瘤经过再次姑息消融后,仅1个肿瘤引起的疼痛获得了完全缓解。局部有效率为87.2%(34/39个肿瘤)。肿瘤大小(以5 cm作为截断值)是唯一与局部有效呈显著相关的因素(P=0.002)。生存时间：中位随访期为17.7月(范围6-45月),首次消融后中位随访期为10.8月(范围3-36月)。消融后1月时评价为局部有效的34个肿瘤中,5个肿瘤(14.7%)在末次随访中评价为局部进展,消融相关中位局部控制时间为10.6月(范围2.4-35.3月)。未发现与消融相关局部控制时间呈显著相关的预后因素。25例(71.4%)患者最终出现疾病进展,包括局部肿瘤进展5例和远处转移20例。消融相关无进展生存时间为5.4月(范围0.7-35.3月),总无进展生存时间为11.8月(范围3.244.7月)。局部有效与消融相关无进展生存时间呈显著相关(P=0.003)。达最佳总疗效至首次消融的时间间隔与无进展生存时间呈显著相关(P=0.011)。14例(40.0%)患者最终死亡,死因包括肺内进展5例、远处转移8例、呼吸系统疾病(慢性阻塞性肺疾病急性加重)1例,9例(25.7%)为无进展存活。消融相关总生存时间为10.6月(范围3.1-36.2月),总生存时间为17.7月(范围545月)。局部有效与消融相关总生存时间(P=0.000)及总生存时间(P=0.001)均呈显著相关。并发症：无操作相关死亡病例,无操作30天内死亡病例。主要并发症发生率为12.8%,包括需要闭式引流的症状性气胸(n=2)、支气管胸膜瘘(n=1)以及需要使用抗生素的肺炎(n=2)。次要并发症发生率为38.5%,包括无症状性的少量气胸(n=6)、胸腔积液(n=6)及出血(n=3)。不良反应发生率为59%,包括1-2级疼痛(n=2)及消融后综合征(n=14)。次要并发症和不良反应的耐受性良好。结论：1)一线治疗后的进展期非小细胞肺癌采用微波消融维持治疗,既能获得局部控制,也能带来生存获益；2)作为维持治疗的新手段,微波消融能够延长生存时间、且并发症耐受性良好,优于传统维持治疗手段；3)微波消融的确切局部疗效以及早期干预与生存获益显著相关。因此,影像引导下经皮微波消融作为一线治疗后的进展期非小细胞肺癌患者的维持治疗新手段是安全、有效的。
[Abstract]:Objective: lung cancer is the main cause of death of cancer worldwide, China is the world's first lung cancer lung cancer in our country, cancer incidence and mortality in the first place. Non small cell lung cancer accounts for 89%. of all lung cancer cases of non-small cell lung cancer lost the chance for radical surgery, the systemic chemotherapy is the main treatment method. However, the traditional first-line treatment has reached the effect of platform, the total remission rate of 25%-35% disease progression time was 3-5 months, the median survival time of 8-10 months, 1 year survival rate of 30-40%, the 2 year survival rate of 10-15%. in most patients appeared in the first-line treatment period, even after the first-line therapy to relieve or stable, finally inevitably progress, therefore, the overall prognosis is poor. For the first-line treatment to relieve or stable, using non platinum based cytotoxic drugs or targeted therapy can be In order to delay the progress. However, maintenance treatment application is the first-line treatment of drug toxicity and physical condition limit, long-term maintenance treatment of patients with poor tolerance; maintain the curative effect of the treatment effect by first-line therapy, pathological types, gene mutation (fusion) of the impact; although studies have shown that maintenance therapy can prolong progression free survival time. But there is no strong evidence it can significantly prolong survival time; the curative effect of maintenance therapy is not superior to the second-line treatment after disease progression. Energy is the use of thermal or non thermal ablation directly destroy local tumor treatment. Among them, microwave ablation is the electromagnetic wave in the frequency range between 300 MHz-300 to GHz tumor cells produce heat injury so as to induce the change of coagulation treatment. CT guided percutaneous microwave ablation is a new kind of security, there are Lung cancer, minimally invasive treatment effect, can reduce the risk of local recurrence, and the curative effect is not affected by the histological type and gene mutation (fusion) effect. Therefore, it can be used for first-line treatment or partial remission or stable patients, to further eliminate the residual tumor cells, reduce local recurrence, to prolong the survival time, to improve the quality of life. The purpose of this study was to evaluate CT guided percutaneous microwave ablation as the first-line treatment after partial remission or stable advanced non-small cell lung cancer patients to maintain the safety and effectiveness of the new treatment methods, and to explore the factors related to the prognosis. Materials and methods: in all IIIB and IV January 2010 - March 2014 to obtain pathological diagnosis of patients with non-small cell lung cancer, including some early radical surgery recurrence and (or) transfer for a period of progress. The cases. All patients received standard chemotherapy for first-line treatment: two platinum drug standard scheme, repeated every 21 days for a cycle, a total of 4-6 cycles; with the epidermal growth factor receptor sensitive mutation in patients with targeted therapy; IIIB patients received concurrent chemotherapy and sequential chemotherapy. The efficacy of solid tumor evaluation. The standard version of >1.1 used to evaluate after first-line therapy. According to the partial remission or stable patients by multidisciplinary assessment after microwave ablation therapy. CT guided percutaneous microwave ablation of optimizationthe, anesthesia with local anesthesia combined with preemptive analgesia, strictly implement the technical specifications of aseptic operation. In order to make the ablation region overlap to form the ablation zone is large enough or conformal, according to the different tumor size there are mainly three kinds of ablation mode: 3 cm small tumor diameter less than single needle single point mode; the diameter of 3-5 cm The medium size tumor by using single needle multipoint mode; the diameter of 5 cm large tumor should adopt multi needle multipoint mode. The microwave antenna puncture reached the target tumor at the bottom, and according to the change of the ablation process of CT image adjusting microwave antenna position and depth, until the target tumor was completely covered and around the ablation zone safety margin of 5-10mm wide or reaches the preset imaging end point so far. After the first ablation, ablation needle tract before removal of the microwave antenna in order to avoid needle tract bleeding, tumor. In order to enhance the CT as the baseline data of new ablation in January, after the March review of enhanced CT, standard terminology and Reporting Standards > evaluation by under the guidance of tumor ablation image ablation. < < the complications of common adverse events evaluation standard >4.03 version of the report. Results: after first-line treatment, 19 cases (54.3%) for evaluation of the effectiveness of partial remission, 16 cases of curative effect evaluation Stable. 39 tumors in 35 patients were 39 times of microwave ablation. Among them, 3 times and 2 tumor ablation treatment, 3 patients with 3 tumors were 2 ablation. All 39 ablations were according to the norms of operation, technical success rate of 100%.26 ablation using single microwave antenna the operation, 13 ablation using two microwave antenna operation. The median ablation power is 70 W (60-75 W), the median duration of ablation time was 7 minutes (range 3-15 minutes). Median time interval was the best overall response to the first ablation for January (7 days -22 months). The local effect: for the first time in January 32 after ablation, the tumor (82.1%) achieved a complete ablation, 7 tumors (17.9%) incomplete ablation. 1 of them did not complete ablation of the tumor after repeat ablation achieved complete ablation; the other 2 palliative pain effect after palliative tumor ablation, only 1 tumors cited The pain was completely relieved. The local rate was 87.2% (34/39 tumor). Tumor size (up to 5 cm as cutoff value) is the only effective factors were significantly correlated with local (P=0.002). The survival time: the median follow-up period was 17.7 months (range 6-45 months), for the first time after ablation in position the follow-up period was 10.8 months (range 3-36 months). After ablation January 34 assessment of local tumor effectively in 5 tumors (14.7%) at the last follow-up evaluation for local ablation in progress, related local control time was 10.6 months (range 2.4-35.3 months). No local financial and consumer the control time was significantly related to prognostic factors in.25 cases (71.4%) patients had disease progression, including 5 cases of local tumor progression and metastasis in 20 cases. The ablation related progression free survival time was 5.4 months (range 0.7-35.3 months), the total progression free survival time was 11.8 months (range 3.244.7 months). There are local Effect of ablation related progression free survival time was significantly correlated (P=0.003). The total effect for the first time to reach the best ablation time interval and progression free survival time was significantly correlated with.14 (P=0.011) (40%) patients died, including 5 cases of death in lung metastasis, 8 cases of acute exacerbation of chronic respiratory disease (obstructive pulmonary disease) in 1 cases, 9 cases (25.7%) for progression free survival. Ablation related total survival time was 10.6 months (range 3.1-36.2 months), the total survival time was 17.7 months (range 545 months). With effective local ablation related survival time (P=0.000) and overall survival (P=0.001) were significant. Complications: no dead cases, no operation death within 30 days. The complication rate was 12.8%, including the need to close the symptoms of pneumothorax drainage (n=2), bronchopleural fistula (n=1) and the need to use antibiotics for pneumonia (n=2) and secondary. The incidence rate of complication was 38.5%, including pneumothorax asymptomatic (n=6), pleural effusion (n=6) and hemorrhage (n=3). The incidence of adverse reaction was 59%, including 1-2 levels of pain (n=2) and ablation syndrome (n=14). The tolerance of minor complications and adverse reactions. Conclusion: 1) small cell lung cancer treated by microwave ablation of maintenance therapy in advanced first-line treatment after, can obtain the local control, also can bring survival benefit; 2) as a maintenance treatment, microwave ablation can prolong the survival time, complications and well tolerated treatment are higher than those of traditional maintenance; 3) were significantly related to the exact the local effect of microwave ablation and early intervention and survival benefit. Therefore, CT guided percutaneous microwave ablation in the treatment of a progression after first-line treatment of non-small cell lung cancer patients is safe and effective.

【学位授予单位】：山东大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R734.2

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