本文關(guān)鍵詞： 非小細(xì)胞肺癌 CT引導(dǎo)下經(jīng)皮微波消融 無進(jìn)展生存時(shí)間 總生存時(shí)間　出處：《山東大學(xué)》2016年博士論文　論文類型：學(xué)位論文

【摘要】：目的：肺癌是世界范圍內(nèi)癌癥的主要死因,中國是世界第一肺癌大國,肺癌居我國癌癥發(fā)病率和死亡率的首位。非小細(xì)胞肺癌占全部肺癌病例的89%。進(jìn)展期非小細(xì)胞肺癌失去了根治性手術(shù)的機(jī)會(huì),目前以系統(tǒng)化療為主要治療手段。然而,傳統(tǒng)一線治療已經(jīng)達(dá)到了療效平臺(tái),總緩解率25%-35%,疾病進(jìn)展時(shí)間3-5月,中位生存時(shí)間8-10月,1年生存率30-40%,2年生存率10-15%。大多數(shù)患者在一線治療期間就出現(xiàn)了進(jìn)展,即使是經(jīng)一線治療達(dá)到緩解或穩(wěn)定的患者,最終也不可避免地出現(xiàn)進(jìn)展,因此,總體上患者預(yù)后極差。對(duì)于經(jīng)一線治療達(dá)到緩解或穩(wěn)定的患者,采用非鉑類細(xì)胞毒藥物或靶向藥物維持治療可以延遲進(jìn)展。然而,維持治療的應(yīng)用受到一線治療藥物毒性和體力狀況的限制,長期維持治療患者耐受性差；維持治療的療效受到一線治療療效、組織病理類型、基因突變(融合)情況的影響；盡管有研究證實(shí)維持治療能夠延長無進(jìn)展生存時(shí)間,但沒有強(qiáng)烈證據(jù)證實(shí)其能夠顯著延長總生存時(shí)間；維持治療的療效并不優(yōu)于在疾病進(jìn)展后才開始的二線治療。能量消融是采用熱或非熱方式直接消滅局部腫瘤的治療方式。其中,微波消融是采用頻率范圍在300 MHz-300 GHz之間的電磁波對(duì)腫瘤細(xì)胞產(chǎn)生高溫?zé)釗p傷從而誘導(dǎo)其凝固性改變的治療方式。影像引導(dǎo)下經(jīng)皮微波消融是一種新興的安全、有效的肺癌微創(chuàng)治療手段,可以降低腫瘤的局部復(fù)發(fā)風(fēng)險(xiǎn),且其療效不受組織病理類型和基因突變(融合)情況影響。因此,或可用于經(jīng)一線治療達(dá)到部分緩解或穩(wěn)定的患者,進(jìn)一步消滅殘留腫瘤細(xì)胞、減少局部復(fù)發(fā),最終達(dá)到延長生存時(shí)間、改善生活質(zhì)量的目的。本研究旨在評(píng)價(jià)CT引導(dǎo)下經(jīng)皮微波消融作為經(jīng)一線治療后達(dá)到部分緩解或穩(wěn)定的進(jìn)展期非小細(xì)胞肺癌患者的維持治療新手段的安全性和有效性,并探索相關(guān)預(yù)后因素。材料和方法：納入2010年1月——2014年3月之間獲得病理學(xué)確診的全部IIIB期和IV期非小細(xì)胞肺癌患者,其中包括部分早期根治性手術(shù)后復(fù)發(fā)和(或)轉(zhuǎn)移再分期為進(jìn)展期的病例。所有患者接受標(biāo)準(zhǔn)一線治療：化療方案為含鉑兩藥標(biāo)準(zhǔn)方案,每21天重復(fù)為一周期,共4-6周期；具有表皮生長因子受體敏感突變的患者接受靶向治療；IIIB期患者接受同步放化療序貫化療。一線治療后采用《實(shí)體瘤療效評(píng)價(jià)標(biāo)準(zhǔn)》1.1版評(píng)價(jià)療效。針對(duì)其中達(dá)到部分緩解或穩(wěn)定的患者由多學(xué)科評(píng)估后接受微波消融治療。經(jīng)皮微波消融操作全程在CT引導(dǎo)下進(jìn)行,麻醉采用局麻聯(lián)合超前鎮(zhèn)痛方式,嚴(yán)格執(zhí)行無菌操作技術(shù)規(guī)范。為了使各消融區(qū)域重疊以形成足夠大或適形的消融區(qū)域,根據(jù)腫瘤大小的不同主要有三種消融模式：①直徑≤3 cm的小腫瘤采用單針單點(diǎn)模式；②直徑3-5 cm的中等大小腫瘤采用單針多點(diǎn)模式；③直徑5 cm的大腫瘤應(yīng)采用多針多點(diǎn)模式。將微波天線穿刺達(dá)靶腫瘤底部,并根據(jù)消融過程中CT圖像的變化適當(dāng)調(diào)整微波天線的位置和深度,直至靶腫瘤完全被消融區(qū)域覆蓋且圍繞以5-10mm寬的安全邊緣或達(dá)到預(yù)設(shè)的影像學(xué)終點(diǎn)為止。消融完畢后,要先消融針道后方可拔除微波天線以免針道出血、腫瘤種植。以消融后1月的增強(qiáng)CT作為新的基線資料,以后每3月復(fù)查增強(qiáng)CT,采用《影像引導(dǎo)下腫瘤消融的術(shù)語規(guī)范和報(bào)告標(biāo)準(zhǔn)》評(píng)價(jià)消融療效。并發(fā)癥采用《常見不良反應(yīng)事件評(píng)價(jià)標(biāo)準(zhǔn)》4.03版報(bào)告。結(jié)果：一線治療后,19例(54.3%)療效評(píng)價(jià)為部分緩解,16例療效評(píng)價(jià)為穩(wěn)定。針對(duì)此35例患者的39個(gè)腫瘤進(jìn)行了39次微波消融。其中,3次消融同時(shí)治療2個(gè)腫瘤,3例患者的3個(gè)腫瘤進(jìn)行了2次消融。全部39次消融均按規(guī)范進(jìn)行操作,技術(shù)成功率達(dá)100%。26次消融使用單根微波天線操作,13次消融使用兩根微波天線操作。中位消融功率為70 W(范圍60-75 W),中位消融持續(xù)時(shí)間為7分鐘(范圍3-15分鐘)。達(dá)最佳總療效至首次消融的中位時(shí)間間隔為1月(范圍7天-22月)。局部療效：首次消融后1月,32個(gè)腫瘤(82.1%)達(dá)到完全消融,7個(gè)腫瘤(17.9%)為不完全消融。其中1個(gè)不完全消融的腫瘤經(jīng)過再次消融后達(dá)到了完全消融；另2個(gè)姑息止痛效果不佳的腫瘤經(jīng)過再次姑息消融后,僅1個(gè)腫瘤引起的疼痛獲得了完全緩解。局部有效率為87.2%(34/39個(gè)腫瘤)。腫瘤大小(以5 cm作為截?cái)嘀?是唯一與局部有效呈顯著相關(guān)的因素(P=0.002)。生存時(shí)間：中位隨訪期為17.7月(范圍6-45月),首次消融后中位隨訪期為10.8月(范圍3-36月)。消融后1月時(shí)評(píng)價(jià)為局部有效的34個(gè)腫瘤中,5個(gè)腫瘤(14.7%)在末次隨訪中評(píng)價(jià)為局部進(jìn)展,消融相關(guān)中位局部控制時(shí)間為10.6月(范圍2.4-35.3月)。未發(fā)現(xiàn)與消融相關(guān)局部控制時(shí)間呈顯著相關(guān)的預(yù)后因素。25例(71.4%)患者最終出現(xiàn)疾病進(jìn)展,包括局部腫瘤進(jìn)展5例和遠(yuǎn)處轉(zhuǎn)移20例。消融相關(guān)無進(jìn)展生存時(shí)間為5.4月(范圍0.7-35.3月),總無進(jìn)展生存時(shí)間為11.8月(范圍3.244.7月)。局部有效與消融相關(guān)無進(jìn)展生存時(shí)間呈顯著相關(guān)(P=0.003)。達(dá)最佳總療效至首次消融的時(shí)間間隔與無進(jìn)展生存時(shí)間呈顯著相關(guān)(P=0.011)。14例(40.0%)患者最終死亡,死因包括肺內(nèi)進(jìn)展5例、遠(yuǎn)處轉(zhuǎn)移8例、呼吸系統(tǒng)疾病(慢性阻塞性肺疾病急性加重)1例,9例(25.7%)為無進(jìn)展存活。消融相關(guān)總生存時(shí)間為10.6月(范圍3.1-36.2月),總生存時(shí)間為17.7月(范圍545月)。局部有效與消融相關(guān)總生存時(shí)間(P=0.000)及總生存時(shí)間(P=0.001)均呈顯著相關(guān)。并發(fā)癥：無操作相關(guān)死亡病例,無操作30天內(nèi)死亡病例。主要并發(fā)癥發(fā)生率為12.8%,包括需要閉式引流的癥狀性氣胸(n=2)、支氣管胸膜瘺(n=1)以及需要使用抗生素的肺炎(n=2)。次要并發(fā)癥發(fā)生率為38.5%,包括無癥狀性的少量氣胸(n=6)、胸腔積液(n=6)及出血(n=3)。不良反應(yīng)發(fā)生率為59%,包括1-2級(jí)疼痛(n=2)及消融后綜合征(n=14)。次要并發(fā)癥和不良反應(yīng)的耐受性良好。結(jié)論：1)一線治療后的進(jìn)展期非小細(xì)胞肺癌采用微波消融維持治療,既能獲得局部控制,也能帶來生存獲益；2)作為維持治療的新手段,微波消融能夠延長生存時(shí)間、且并發(fā)癥耐受性良好,優(yōu)于傳統(tǒng)維持治療手段；3)微波消融的確切局部療效以及早期干預(yù)與生存獲益顯著相關(guān)。因此,影像引導(dǎo)下經(jīng)皮微波消融作為一線治療后的進(jìn)展期非小細(xì)胞肺癌患者的維持治療新手段是安全、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.

【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類號(hào)】：R734.2

【相似文獻(xiàn)】

相關(guān)期刊論文 前10條

1 汪青蓉;;經(jīng)皮微波消融治療膈頂肝癌的護(hù)理[J];中國當(dāng)代醫(yī)藥;2012年10期

2 程祥勇;于曉玲;謝道林;張德東;;超聲引導(dǎo)下經(jīng)皮微波消融肝表面腫瘤的臨床應(yīng)用[J];軍醫(yī)進(jìn)修學(xué)院學(xué)報(bào);2012年06期

3 李欣;劉衛(wèi)星;李春伶;盛林;魯通;梁萍;董寶瑋;;經(jīng)皮微波消融活體兔肺的實(shí)驗(yàn)研究[J];醫(yī)學(xué)影像學(xué)雜志;2012年06期

4 董寶瑋;梁萍;于曉玲;于德江;張晶;馮蕾;程志剛;王e，

本文編號(hào)：1497856