小细胞肺癌概况与治疗进展

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,2020/11/3,*,小细胞肺癌概况及治疗进展,2020/11/3,1,流行病学,小细胞肺癌每年新发病人数占肺癌的20%左右（15%25%）。,在肺癌所有组织类型中，小细胞 肺癌的发病与吸烟的关系最为密切，只有3%无既往吸烟病史。,吸烟与肺癌的关系：吸烟者20% 终生将会患肺癌，肺癌病人中80%与吸烟有关。,肺癌病人中吸烟者比不吸烟者死亡危险高820倍。,2020/11/3,2,生物学行为特征,小细胞肺癌是肺癌中分化最低、性质最恶的一型。细胞来源是Kulchisky细胞（K细胞，神经内皮细胞），小细胞肺癌的神经内分泌综合征就是由于细胞浆内的Kulchisky颗粒，组织化学证明，颗粒具有嗜银性和亲银性，是一种化学感受器。小细胞肺癌具有倍增时间短（33天）、增值指数高、浸润性生长及较早发生转移等特点。通常发生于大支气管内，但也发生于外周支气管。,2020/11/3,3,病理,肿块较大，切面灰白色，鱼肉状。小细胞肺癌很少形成空洞，但常有坏死和出血灶。不宜对小细胞肺癌进行分级，因为所有小细胞肺癌都属于高级别。,SCLC,有,3,个亚型（单纯型，中间型、混合型）。近年来，不同组织类型肺癌之间的转变，引起学术界的重视。有的病人放化疗后又接受了手术，术后病理有改变，有的病例经病理检查证实为小细胞肺癌，,510,年后复发，病理检查为鳞癌。复合性小细胞肺癌是小细胞肺癌与另外一种成分符合组成的癌。,2020/11/3,4,临床表现和诊断,2020/11/3,5,小细胞肺癌的分期,美国老年委员会肺癌研究小组（,VALCSG, Veterans Administration Lung Cancer Study Group,）制定后被国际肺癌研究会修订的分期系统，将小细胞肺癌患者分为两种：局限性肿瘤和广泛性肿瘤。前者为局限于半胸，有区域淋巴结转移（包括肺门、同侧和对侧纵隔、和,/,或锁骨上淋巴结、和,/,或伴癌性胸水）。后者为肿瘤伴对侧胸部和,/,或胸部以外的转移病灶。,VALCSG,分类现在已经被修订的,TNM,分期方法所代替。,2020/11/3,6,预后,小细胞肺癌的自然生存期，广泛性肿瘤平均存活时间不超过,1215,周，局限性肿瘤也只有大约,6,个月。全身化疗的使用使平均存活时间得到了显著的提高，局限性肿瘤为,12,个月，广泛性肿瘤为,910,个月。近年来新的更高生物学活性抗癌药的增加，使小细胞肺癌的生存时间又得到了进一步的延长。,2020/11/3,7,2020/11/3,8,治疗原则,广泛性肿瘤，化疗是最基本的治疗手段，然后是对症治疗。,局限性肿瘤，则需要选择多模式的治疗方案。,2020/11/3,9,广泛型病例的化疗,大约,2/3 SCLC,病人确诊时为广泛期病变,80,年代以前方案被当作标准治疗的方案,其后,方案代替方案保持了,10,年不动的标准治疗地位,在方案的基础上加,1,个药的,3,药联用方案、,/,交替治疗、大剂量导入疗法、大剂量巩固疗法、周剂量冲击疗法等众多的方案均未使方案疗效有更多的进步,2020/11/3,10,广泛型病例的化疗,进入90年代,广泛型小细胞肺癌的治疗方针定为:,标准方案为方案;,不适于方案者可以方案、方案、卡铂+方案代替;,治疗疗程为方案4个周期,、方案6个周期为1疗程,这些方案确可延长患者的生命,但几乎全部的病例均复发,中位生存期为810个月,3年生存率仅有百分之几,2020/11/3,11,广泛型病例的化疗,为了使小细胞肺癌的疗效进一步提高,必须发展高效的抗癌药并确立更有力的化疗方案。90年代以后异环磷酰胺、长春瑞宾、拓扑替康、依林特肯( 11)、紫杉醇以及吉西他宾等逐渐用于SCLC的临床研究,对无论是经治病例还是初治病例均有良好的疗效 。,2020/11/3,12,广泛型病例的化疗,等报告在 11和联合方案期临床实验中,进展型病例35例中率35%,中位生存期13个月,疗效良好。,日本临床癌研究组肺癌内科小组于1995年开始了由日本全国多家医院设施参加的方案与方案治疗进展型肺小细胞癌的临床比较实验。本实验预定3年完成230例,在完成了144例时进行分析就得到了疗法比疗法疗效更明显的结果,故提前结束了实验,此后的追踪结果也显示方案明显优于方案,二者的中间生存期分别为13个月、9个月,2年生存率分别为18. 9%、6. 5%。,2020/11/3,13,广泛型病例的化疗,这一划时代意义的结果在2000年美国临床肿瘤学会上一经发表,即引起了世界的瞩目,美国为验证这一结果,后来进行了2项有关的期临床实验。虽然实验结果尚未得到,还没有得到世界的公认,但在日本已经将方案作为了治疗广泛型小细胞肺癌的标准治疗方案。,2020/11/3,14,局限型病例的治疗,标准治疗是放疗加化疗，另外还存在着手术治疗问题、预防性颅脑放疗问题,在70年代化疗成为小细胞肺癌标准治疗方案时,随着疗效的提高,超过80%的局部复发率也同时成为难解的问题。进入80年代,为增加局部疗效在世界范围内开始实验性加用胸部放疗。总结13个有关比较实验的2103个病例的数据发现,追加胸部放疗可使死亡的危险性减少13%(危险比0 87,95%可信限0 780 94),相当于将3年生存率提高5%(8 .9%14 .9%),由此证明了放疗加化疗的有效性,2020/11/3,15,局限型病例的治疗,90年代,胸部放疗的最佳方案, 是应用每日2次增加每次照射量的加速分割照射()方法。,肺癌内科组对疗法的放化疗同时进行和序贯进行作了比较实验,结果显示放化疗同时进行有能提高生存期的倾向,其中位生存期27个月,3年生存率30%,为当时世界上疗效最好的方案。,同时,在美国还进行了方案加传统的每日1次胸部照射与方案加法胸部照射两种方案的比较实验,结果法的5年生存率及生存期均有明显提高。从此,这一疗法成为了治疗局限型小细胞肺癌不变的标准治疗方案。,2020/11/3,16,SCLC标准化疗方案,经典的联合化疗方案主要有2个,即(、)和(、 16)方案,研究表明对局限期患者,含 16的联合化疗方案的远期疗效优于不含 16的化疗方案,多数临床医生倾向于用或CE方案作为的主要治疗方案。部分医生喜欢用与方案交替化疗,其理论依据是采用无交叉耐药的方案交替化疗有可能减少耐药性的产生,从而提高化疗疗效。尽管两个方案中的药物组成完全不同,但它们并非完全无交叉耐药。临床研究发现,方案化疗失败的患者,采用方案,有效率不到15%,化疗无效的患者,采用方案,则有40%50%的人有效,2020/11/3,17,SCLC标准化疗方案,另一研究报道,将一组广泛期的患者随机分组,一组接受5个周期的(、 6)方案,另一组第1、3、5周期接受方案,第2、4周期接受(、异环磷酰胺、卡铂)方案,结果两组患者的中位生存期没有显著性差异。因此,从目前的研究来看,交替化疗与传统方案的疗效并无本质性差异。,2020/11/3,18,的最佳化疗疗程,有作者进行了较大规模的随机试验,患者先接受5个周期的方案化疗,再随机分组,一组停止化疗,另一组再接受7个周期的化疗,方案不变,两组患者的5年生存率分别为4.1%和4.2%,另一项期试验报道,497名患者接受6个周期的化疗,化疗结束时处于部分或完全缓解的患者再随机分组,一组不再化疗,另一组再接受6个周期的化疗,方案不变。试验结果显示,接受了12个周期化疗的患者其生存期与6个周期的患者相比,并没有延长,2020/11/3,19,的最佳化疗疗程,另有作者报道,将患者随机分组,一组给予3个周期的诱导化疗,另一组给予6个周期的诱导化疗。结果两组的毒副反应、生活质量没有显著性差异,接受6个周期化疗的患者其中位生存期略有提高,但无统计学意义。,对局限期的,国外一般采用同步的化疗加局部放疗。美国东部肿瘤协作组的研究表明,4个周期的化疗加上同步的局部放疗可以达到最佳疗效,增加化疗次数并不能提高疗效。,国内患者一般难以耐受同步放化疗,因此多采用“夹心”法治疗局限期,通常是几个周期化疗结束后给予局部放疗,然后再给予几个周期的化疗。,总之,对于患者,目前一般认为,4,6,个周期的化疗已较为合适,过多的周期并不增加疗效。,2020/11/3,20,的化疗强度,一组患者采用标准剂量的方案化疗,另一组剂量增加,结果两组缓解率、中位生存期和,1,年生存率均无显著性差异,但大剂量组的骨髓毒性明显高于标准剂量组,。,另一项较大规模的期临床研究对广泛期进行了观察,患者随机分组,对照组按标准剂量方案化疗,试验组和的剂量提高,结果两组的有效率和中位生存期没有显著性差异,但大剂量组的毒副反应明显高于对照组。,2020/11/3,21,的化疗强度,对局限期的,情况不尽相同。Ariagada等对局限期的进行了期随机试验,对照组接受标准剂量的、,16,、加胸部放疗,试验组化疗方案相同,只是和的剂量增加,20%,结果试验组的,2,年生存率高于对照组。,国外学者认为,对广泛期的,提高化疗强度并不能提高远期疗效,故不主张盲目增加化疗药物剂量。但对局限期的患者而言,提高化疗强度有可能在一定程度上提高生存率,因此对这类患者,化疗的剂量应接近患者所能耐受的最大剂量。国内部分学者对这一观点持异议。,2020/11/3,22,复发或一线化疗失败患者的治疗,诱导化疗结束后,3,个月内复发或一线化疗无效的患者称为难治性患者。,治疗后复发的患者再次化疗是否有效主要取决于两个因素,:,初次化疗是否有效,尤其是达到过完全缓解的患者再次化疗的有效率较高,;,复发时间距初次化疗结束的时间越短,再次化疗效果越差。对于初次化疗结束后,3,个月内复发的患者,以往的研究表明再次化疗效果不好,有效率很低。,2020/11/3,23,复发或一线化疗失败患者的治疗,对于一线化疗方案无效的患者,采用二线化疗效果也不理想,喜树碱,11(,1,1)+,的有效率为,29%,中位生存期,8,个月。卡铂,+,紫杉醇的有效率为,25%,中位生存期,7,个月,单用拓扑特肯化疗的有效率低于,10%,。此外,还有多种联合化疗方案,但有效率很少超过,20%,但近有文献报道,10,初次化疗采用方案化疗后,3,个月内复发的患者,采用紫杉醇,+,卡铂治疗,有效率高达,30%,这可能是因为方案与紫杉醇,+,卡铂方案无交叉耐药的原因。,2020/11/3,24,复发或一线化疗失败患者的治疗,多数患者复发时通常换用其它方案化疗,但有些患者如诱导化疗效果较好、缓解时间较长,复发时采用原方案化疗仍可获得疗效。,Fujita等报道,一组复发的患者采用DDP+异环磷酰胺+CPT11化疗,每4周重复一次。全组完全缓解1例,部分缓解16例,有效率为94.4%,中位生存时间339天,1年生存率47.5%,度中性粒细胞减少症和血小板减少症的发生率分别是61%和33%。Negoros等报道采用CPT11+VP16治疗复发SCLC,有效率为71%,中位生存期271天。总体而言,对复发者采用何方案进行补救化疗尚无定论,目前的趋势是采用一些含较新药物的联合方案,如CPT11、拓扑特肯、紫杉醇、异环磷酰胺等。,2020/11/3,25,新的化疗药物在中的应用,近十年来,一些新的对非小细胞肺癌有效的化疗药物开始用于的治疗,有拓扑特肯、,11,、双氟胞苷、异长春花碱、紫杉醇等,其中被看好的主要是,11,、拓扑特肯和紫杉醇。各种单药的有效率见表,1,2020/11/3,26,2020/11/3,27, 11,等报道,154名广泛期随机分组,一组采用 11加化疗(组),另一组采用方案化疗,结果组和组的中位生存期分别是12.8月和9.4月(=0.002),2年生存率分别是19.5%和5.2%,组的疗效高于组,组危及生命的骨髓抑制的发生率高于组,但组严重或危及生命的腹泻的发生率高于组。本文引起了人们的极大兴趣,被认为是近20年来化疗的重要进展之一。,2020/11/3,28,Japan:a phase two study,CPT-11 (80 mg/m(2) was given on day1, 8 and 15 every four weeks,ifosfamide (1.5 g/m(2) was given on days 1 through 3 every 4 weeks.,Thirty-four patients (29 men) with a median age of 69 years (range 42-77) and a median Eastern Cooperative Oncology Group (ECOG) performance status of 1 (range 0-2) were enrolled,The response rate was 52.9% with 2 complete responses and 16 partial responses.,2020/11/3,29,拓扑特肯,作为一线化疗,单药的有效率为39%。,一项期临床研究表明,对于曾接受过治疗的,拓扑特肯单药不仅可达到与方案相同的缓解率和生存期,且姑息治疗效果优于方案。,临床上正在尝试一些新的联合化疗方案,如拓扑特肯+或卡铂、拓扑特肯+紫杉醇、拓扑特肯+双氟胞苷、拓扑特肯+异长春花碱等。,拓扑特肯在脑组织中可达到较高的浓度,对曾化疗过的脑转移的有效率为40%63%,完全缓解率13%3%。因此,对初诊时已有脑转移者或为了预防脑转移,拓扑特肯可作为一线化疗药物。,拓扑特肯还具有放射增敏作用。,2020/11/3,30,顺铂+VP16与拓扑特肯 +紫杉醇交替治疗初治广泛期SCLC:北方癌症治疗中心,II,期临床试验,VP16 (100 mg/m(2) on Days 1-3) and 顺铂 (30 mg/m(2) on Days 1-3) on Cycles 1, 3, 5 . topotecan (1 mg/m(2) on Days 1-5) and paclitaxel (200 mg/m(2) on Day 5) on Cycles 2, 4, and 6. Filgrastim support was given with Cycles 2, 4, 6.,70% Grade 4 neutropenia ,23% Grade 4 thrombocytopenia .,Overall toxicities were not different between the two regimens. There were no treatment-related deaths.,Complete or partial responses occurred in 34 patients (77%). The median time to progression was 6.9 months, with a median survival of 10.5 months and with 1-year and 2-year survival rates of 37% and 12%, respectively.,2020/11/3,31,拓扑特肯 +紫杉醇与顺铂+VP16及同步放疗交替治疗初治局限期SCLC:,I,期临床试验,Escalating doses of topotecan (0.8-1.4 mg/m(2) d1-5) and paclitaxel (110-175 mg/m(2) d1) were administered i.v. every 21 days for two cycles,followed by two cycles of etoposide (120 mg/m(2) d1-3) and cisplatin (60 mg/m(2) d1) with thoracic radiotherapy.,Two additional cycles of chemotherapy (topotecan and paclitaxel, followed by etoposide and cisplatin) were given.,2020/11/3,32,The result,grade /=3 neutropenia in 67% of courses of topotecan and paclitaxel and grade /=2 esophagitis in 71% of patients. Two patient died.,Response rates after induction of topotecan and paclitaxel: 16 of 18 (88.8%) partial response, 1 of 18 (5.5%) complete response. Response rates after completion of therapy: 10 of 18 (55.5%) partial response, 7 of 18 (38.8%) complete response.,2020/11/3,33,拓扑特肯日剂量与连续静脉灌注治疗SCLC的,II,期临床,20 case of 1.5 mg/m2 daily for 5 days every 3 weeks . an average of 5 courses (range: 1-13) .,20 case of 1.3 mg/m2 per day over 72 hours administered intravenously every 4 weeks . an average of 2 courses (range: 1-7),2020/11/3,34,拓扑特肯日剂量与连续静脉灌注治疗SCLC的,II,期临床,Confirmed response rates for the daily and continuous-infusion schedules are 62.5% (90% CI: 49-75%) and 15% (90% CI: 1-29%), respectively,grade /=3 neutropenia was 92% (55/60) and grade /=3 leukopenia was 58% (35/60). Nonhematologic toxicity was very mild, with only 10% (6/60) patients experiencing grade4 toxicities.,2020/11/3,35,拓扑特肯联合紫杉醇治疗初治的广泛期SCLC的,II,期临床,untreated ED-SCLC patients ,Eastern Coperative Oncology Group performance status 3 months after first-line chemotherapy) and 12 patients with refractory (R) disease (failed3 months after first-line chemotherapy),2020/11/3,38,健择二线治疗敏感或难治的SCLC,II,期临床,No responses were observed of 24 patients,only three achieved stable disease after six cycles while 21 progressed.,The median time to progression (TTP) was 6 weeks in S group, 5.6 weeks in R group.,the median survival was 8.8 months in S group, 4.2 months in R group.,One-year survival rate was 33.3% in S group, 16.7% in R group.,grade 3/4 neutropenia in 30%, and grade 3 thrombocytopenia in 30%.,2020/11/3,39,多西他赛、健择联合一线治疗广泛期 SCLC,II,期临床,20 case of chemotherapy-naive patients with extensive disease (ED) SCLC,docetaxel 50 mg/m(2) and gemcitabine 1000 mg/m(2), both administered on day 1 and 8 every 3 weeks up to a total of six cycles,A total of 72 cycles was delivered while patients managed to receive the 78 and 84% of the planned dose of docetaxel and gemcitabine,2020/11/3,40,多西他赛、健择联合一线治疗广泛期 SCLC,II,期临床,Only six patients responded partially and the trial ended prematurely since at least seven responses were required among the first 19 patients,median time to progression (TTP) was 8 months and median survival 9.6 months,Hematological and non-hematological toxicity was generally acceptable,In conclusion, docetaxel-gemcitabine showed a modest response rate in chemotherapy-naive patients with ED SCLC,2020/11/3,41,东方癌症协作组1597试验：健择治疗难治、复发 SCLC,II,期临床,SCLC patients with measurable disease had treated with one prior chemotherapy regimen,Patients were required to have Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 and adequate organ function,gemcitabine 1,000 mg/m2 on days 1, 8, and 15 of a 28-day cycle.,2020/11/3,42,东方癌症协作组1597试验：健择治疗难治、复发 SCLC,II,期临床,20 refractory and 26 sensitive patients,Forty-two of these patients were assessable for response and survival, and 44 were assessable for toxicity,3/4 hematologic toxicities 27%, 3/4 nonhematologic toxicities 9% and neurologic toxicity 14%,Objective response rate were 11.9%, including one patient with refractory SCLC and four patients with sensitive SCLC. Median survival for the overall group was 7.1 months , no significant different for two group.,2020/11/3,43,健择、顺铂、VP16治疗初治的SCLC,I/,II期临床试验,gemcitabine (1000 mg/m(2) on days 1 and 8) ，cisplatin (70 mg/m(2) on day 2) ，etoposide (50 mg/m(2) on days 3, 4, and 5) every 3 weeks.,No prophylactic granulocyte colony-stimulating factors were used,56 patients with limited- or extensive-stage SCLC （8 for phase I),2020/11/3,44,健择、顺铂、VP16治疗初治的SCLC,I/,II期临床试验,Ten complete and 29 partial responses were reported, for an overall response rate of 72.2%,The median duration of response and median survival were 8.0 and 10 months, respectively,1-year survival probability of 37.5%,Grade 3/4 neutropenia and thrombocytopenia occurred in 66.7% and 53.7%, respectively .Non-hematologic toxicity was mild,2020/11/3,45,健择、长春瑞宾治疗难治或复发SCLC,II期临床试验,All patients received previous platinum/etoposide combination chemotherapy; in addition, 12 patients received paclitaxel as part of their first-line therapy,gemcitabine 1000 mg/m2 and vinorelbine 20 mg/m2 on days 1, 8, and 15 of each 28-day cycle,Patients were reevaluated for response after two cycles of therapy; those with objective response or stable disease continued treatment for six courses or until disease progression.,2020/11/3,46,健择、长春瑞宾治疗难治或复发SCLC,II期临床试验,Three of 28 evaluable patients (10%) had partial responses. None of the 17 patients with refractory disease responded, while 3 of 12 patients (25%) with relapsed disease had partial responses,Median survival was 5 months,The activity of gemcitabine and vinorelbine in patients with previously treated small cell lung cancer is modest and is limited to patients with relapsed (versus refractory) disease,2020/11/3,47,长春瑞宾、阿霉素治疗复发SCLC,II期临床试验：CALGB 9332,vinorelbine at 25 mg/m2 on days 1 and 8 and doxorubicin at 50 mg/m2 on day 1 of each 21-day cycle,The trial was stopped early because of excessive toxicity,The partial response rate was 26.7%,Toxicities included grade IV neutropenia in 73%, and febrile neutropenia and/or sepsis in 60%,2020/11/3,48,标准剂量和高剂量VP16、IFO、DDP、ADM联合化疗治疗100例SCLC：一个完善的随访报告,Standard-dose chemotherapy (SDC) consisting of etoposide (500 mg/m2), ifosfamide (4000 mg/m2), cisplatin (50 mg/m2) and epirubicin (50 mg/m2) (VIP-E), followed by granulocyte colony-stimulating factor (G-CSF), was given to 100 patients with SCLC,2020/11/3,49,标准剂量和高剂量VP16、IFO、DDP、ADM联合化疗治疗100例SCLC：一个完善的随访报告,Thirty patients with qualifying responses to VIP-E proceeded to high-dose chemotherapy (HDC) with autologous peripheral blood stem-cell transplantation (PBSCT) after etoposide (1,500 mg/m2), ifosfamide (12,000 mg/m2), carboplatin (750 mg/m2) and epirubicin (150 mg/m2) (VIC-E) conditioning.,2020/11/3,50,RESULTS OF STANDARD-DOSE VIP-E,Ninety-seven patients were evaluable for response,The objective response rate was 81% in LD SCLC (33% CR, 48% PR),77% in ED SCLC (18% CR, 58% PR).,The median survival was 19 months in LD SCLC and 6 months in ED SCLC,The five-year survivals were 36% in LD and 0% in ED SCLC,The treatment-related mortality was 2%. Two additional patients in CR from their SCLC developed secondary NSCLC),2020/11/3,51,RESULTS OF HIGH-DOSE VIC-E,HDC was feasible in 16% of ED-, and 58% of LD-patients.,The median survivals were 26 months in LD SCLC, and 8 months in ED SCLC,The five-year survival was 50% in LD and 0% in ED,Four patients died of early treatment-related complications (TRM 13%). Two additional patients in CR from their SCLC developed secondary malignancies (esophageal cancer, secondary chronic myelogenous leukemia).,2020/11/3,52,手术在小细胞肺癌治疗中的地位,近年对外科手术在治疗局限期小细胞肺癌中的地位有了重新的认识。现有资料认为采用综合治疗力争根治性切除是使患者长期存活的重要治疗模式。化、放疗仍是小细胞肺癌的主要治疗手段,手术应掌握适应证。总的策略是在术前诱导化疗的基础上手术,辅以必须的术后化疗。手术能够完全切除的,术后应进行预防性颅脑照射。对于术中发现肺门和纵隔淋巴结转移的,建议术后纵隔放疗,2020/11/3,53,手术在小细胞肺癌治疗中的地位,在,1973,年英国医学研究会发表了一项研究结果后,当时医学界普遍认为外科手术不适合治疗,这项研究将,144,例没有发现胸外转移的患者随机分组进行手术和放疗,也可以转为或同时配合应用其他治疗方法。结果发现手术组,(,包括切除和未能切除的例数,),的,5,年绝对生存率为,1%,而放疗组为,4%,。放疗组的中位生存期明显长于手术组,(10,个月比,7,个月,;,=0 04),。迄今为止,这是惟一一个手术作为基本治疗方法的随机试验研究,2020/11/3,54,手术在小细胞肺癌治疗中的地位,后来,由于联合应用放化疗治疗的失败率较高、治愈率较低,大家不得不重新认识手术在治疗中的地位,把手术作为基本治疗的研究中,患者近乎半数病例术前没有诊断而术后病理证实为。在这些研究中,仅有,10%,患者采用了手术作为基本治疗的治疗方案,3,4,。多数的患者处于或期,其中位生存期接近,2,年,5,年生存率为,20%,27%,2020/11/3,55,手术在小细胞肺癌治疗中的地位,手术适应证有学者研究了在经过化疗辅以胸部放疗和的综合治疗后手术治疗的作用。试验初期共有,328,例患者入选。将其中,146,例化疗反应正常的患者随机分为,2,组,:,手术组,70,例,非手术组,76,例。全部患者都经支气管镜活检证实为。手术组和非手术组的,2,年生存率没有差异。手术组的中位生存期为,15,个月,非手术组为,19,个月。局部病变控制率没有差异。,2020/11/3,56,手术在小细胞肺癌治疗中的地位,等进行一项综合治疗期小细胞肺癌的期临床试验研究却得出另一个结论。共有,46,例患者入组,其中进行放、化疗和手术联合治疗的,24,例,(,期,2,例,),23,例完全切除。完全切除组的,5,年生存率为,63%,局部病变复发率为,0,。这样就提出了一个手术适应证的问题,2020/11/3,57,2020/11/3,58,预防性颅脑放疗,脑是小细胞肺癌常见的转移部位，脑转移的发生率高达50%。多药联合化疗和放射治疗的应用，长期生存率提高，脑转移的发生也随之增加。文献报道，治疗后生存6年以上的病例中枢神经系统复发率高达80%。检索发现一个有关脑预防照射的系统评价结果PCI综合分析协作组对SCLC完全缓解病例PCI随机对照研究资料进行荟萃分析，共7个RCT研究，987例患者。结果显示，.SCLC完全缓解病例脑预防照射能够提高生存率和无病生存率（DFS）。PCI组3年生存率提高了5.4%。与对照组比较，PCI组死亡的相对危险性（RR）为0.84。,2020/11/3,59,结论,目前化、放疗仍是小细胞肺癌的主要治疗手段。手术作为一种治疗手段应该掌握其适应证。对于术前用分期定为期、期以及部分期的小细胞肺癌患者,应该采用术前诱导化疗,+,手术,+,必须的术后化疗的治疗方式,术中尽可能少输血及尽可能清除淋巴结。对于手术能够完全切除的患者,可以改善预后、降低脑转移的发生率。对于术中发现肺门和纵隔淋巴结转移的,建议术后纵隔放疗。对于其他的化疗无效的局限期患者,也应争取尽可能的手术切除,因其病变中可能有非小细胞成分。对于局限期小细胞肺癌患者,治疗超过,18,个月到,2,年后,出现孤立性复发时也应考虑手术治疗。总之,采用综合治疗力争根治性切除是使小细胞肺癌患者长期存活的重要治疗模式,2020/11/3,60,