非小细胞肺癌根治术后放射治疗价值的前瞻性研究
中国肺癌杂志 2000年第5期第3卷 肺癌放射治疗专刊
作者:冯勤富 汪楣 汪良骏 杨宗贻 张汝刚 张大为 殷蔚伯
单位:冯勤富 汪楣 杨宗贻 殷蔚伯(中国医学科学院协和医科大学肿瘤医院放疗科 北京,100021);汪良骏 张汝刚 张大为(胸外科)
关键词:肺肿瘤;术后放疗;手术治疗
【摘要】目的 评价术后放疗对根治术后N1与N2非小细胞肺癌的作用。方法 1982年2月至1995年12月收治的366例小于65岁的N1与N2非小细胞肺癌病例,随机分为术后放疗组(n=184)和单纯手术组(n=182)。结果 术后放疗组和单纯手术组5年生存率分别为43.4%±5.1%和40.5%±4.6%(P=0.56),5年无瘤生存率分别为42.9%±5.2%和38.3%±4.5%(P=0.28)。T3-4N1M0患者在术后放疗组的5年生存率和5年无瘤生存率分别为58.1%±15.5%和65%±12%,单纯手术组则分别为39.9%±10.2%(P=0.092)和40%±10%(P=0.057)。术后放疗可明显减少胸内复发(P<0.01)。结论 术后放疗可减少局部复发,对总的生存改善不明显,但对T3-4或N1患者有望获得治疗益处。
【中图分类号】R730.55;R734.2
A randomized clinical trial of postoperative radiotherapy of the patients with non-small cell lung cancer after radical surgery
FENG Qinfu,WANG Mei,WANG Liangjun,YANG Zongyi,ZHANG Rugang,ZHANG Dawei,YIN Weibo
(Department of Radiation Oncology,Cancer Hospital,Chinese Academy of Medical Sciences & Peking Union Medical University,Beijing 100021,P.R.China)
【Abstract】Objective To study the value of postoperative radiotherapy of non-small cell lung cancer (NSCLC) with lymph node metastasis (N1 to N2) after radical surgery.Methods From February,1982 to December,1995,three hundred and sixty-six patients with NSCLC with N1 or N2 disease were randomized into postoperative radiation group (S+R) and surgery alone group (S alone).Radiation fields covered the ipsilateral hilum and most part of mediastinum.The mid-plane dose was 60Gy/30fx for 6 weeks.One hundred and thirty-four patients in S+R and 162 patients in S alone were available for analysis.Clinical data of the two groups were comparable in both arms,except for the numbers of patient with N2 disease.Results The overall 5-year survival rates of S+R group and S alone group were 43.4%±5.1% and 40.5%±4.6%(P=0.56) respectively.The 5-year disease-free survival rates were 42.9%±5.2% in S+R and 38.3%±4.5% in S alone (P=0.28) respectively.The overall 5-year survival rate and 5-year disease-free survival rate of patients with T3-4N1M0 disease were 58.1%±15.5% and 65%±12% in S+R group,and 39.9%±10.2%(P=0.092) and 40%±10%(P=0.057) in S alone.There was less loco-regional recurrence in S+R than in S alone (P<0.01).Distant metastasis was similar in the two groups.Conclusion Postoperative radiation has a significant impact in decreasing local relapse,but not in overall survival.However,it may be benefit to those patients with advanced local diseases (T3-4) and early N disease (N1).
【Key words】Lung neoplasms Postoperative radiotherapy Surgery
肺癌是人类癌症死亡的主要病因之一,大约80%的肺癌为非小细胞肺癌(NSCLC),外科是首选治疗方法,然而不到1/3的患者适宜于根治手术。目前术后5年生存率仅为25%左右。为了评价NSCLC术后放疗的临床意义,我院将根治术后病理为N1或N2的NSCLC患者进行前瞻性临床研究,现报告结果如下。
1 材料与方法
1.1 一般资料 自1982年2月至1995年12月,366例年龄小于65岁,根治术后病理为N1或N2的NSCLC患者进行随机分组,分为术后放疗组(184例)和单纯手术组(182例)。在术后放疗组中,除外拒绝放疗29例,放疗前、中期出现远处转移未完成放疗者5例,术后1月内死亡1例,其它原因未完成放疗者5例(<40Gy),非根治术和无淋巴结转移各1例以及丢失病历8例,共134例入组分析。在单纯手术组中,除外自行放疗或化疗者10例(治疗时无复发与转移),术后即刻发生胸外转移2例以及病历丢失8例,共162例入组分析。
1.2 治疗方法 术后2~4周进行放疗,用60Co、6MV或8MV-X放疗同侧肺门和相应纵隔淋巴结引流区,前后野放射剂量40Gy后,避开脊髓,直至总量为60Gy。除少数有1、2区淋巴引流区转移者进行锁骨上区预防性放疗(50Gy)外,锁骨上区不进行预防性放疗。
1.3 统计学处理 随诊截止至1997年10月。采用Kaplan-Meier方法统计生存率,Log-rank进行检验,其他统计学分析采用χ2检验。
2 结果
如表1所示,一般临床资料中,除术后放疗组N2患者比例稍高外,其它各项临床资料两组间比较无显著性差异(P>0.05)。
表 1 入组患者临床资料
Tab 1 General characteristics of the studied patients
Items |
n(%) |
P value |
S alone |
S+R |
Total cases |
162 |
134 |
Male |
122(75.3) |
102(76.1) |
Female |
40(24.7) |
32(23.9) |
Median age(years) |
55 |
55 |
P-TNM |
|
|
P<0.05 |
Ⅱ |
82(50.6) |
52(38.8) |
ⅢA |
74(45.7) |
78(58.2) |
ⅢB |
6(3.7) |
4(3.0) |
P-N |
|
|
P<0.05 |
N1 |
118(72.8) |
73(54.5) |
N2 |
44(27.2) |
61(45.5) |
P-T |
T1-2 |
117(72.2) |
97(72.4) |
T3-4 |
45(27.8) |
37(27.6) |
Histology |
Squamous cell carcinoma |
89(54.9) |
76(56.7) |
Adenocarcinoma |
64(39.5) |
48(35.8) |
Others |
9(5.6) |
10(7.5) |
Extent of resection |
Lobectomy |
89(54.9) |
68(50.7) |
Bilobectomy |
23(14.2) |
27(20.1) |
Pneumonectomy |
50(30.9) |
39(29.1) |
2.1 两组生存情况(图1) 3年和5年总的生存率在术后放疗组分别为51.9%±4.7%和43.4%±5.1%,单纯手术组为50.2%±4.3%和40.5%±4.6%(P=0.56)。3年和5年无瘤生存率术后放疗组为50.7%±4.7%和42.9%±5.2%,单纯手术组为44.4%±4.3%和38.3%±4.5%(P=0.28)。
图1 两组患者总的生存率(A)和无瘤生存率(B)
Fig 1 Overall survival rates and disease-free survival rates of the patients in the two groups
2.2 亚组分析结果(表2) 在分组为Ⅲ期、N1以及T3-4的患者中,术后放疗组的疗效较单纯手术组有增高的趋势,但经统计学处理无显著性差异。在T3-4N1M0的患者中,术后放疗组(23例)的3年和5年生存率分别为72.7%±10.6%和58.1%±15.5%,单纯手术组(33例)分别为46.6%±9.5%和39.9%±10.2%(P=0.092);术后放疗组3年和5年无瘤生存率为74%±10%和65%±12%,单纯手术组分别为46%±10%和40%±10%(P=0.057)(图2)。
表 2 影响生存结果的因素分析
Tab 2 Analysis of factors influencing survival results
Factor |
Survival rate(%) |
P value |
S alone |
S+R |
3-year |
5-year |
3-year |
5-year |
TNM stage |
Ⅱ |
58.4±5.9 |
49.4±6.3 |
60.4±7.2 |
54±7.7 |
0.9509 |
Ⅲ |
41.8±6 |
31.1±6.1 |
45.7±6.3 |
34.3±6.8 |
0.2891 |
T3-4N1M0 |
46.6±9.5 |
39.9±10 |
72.7±11 |
58.2±15.5 |
0.0918 |
Lymph node status |
N1 |
55.1±5.1 |
46.7±5.4 |
63.6±6 |
56.1±6.7 |
0.288 |
N2 |
35.9±7.6 |
23±7.2 |
35.9±7.2 |
26.1±7.1 |
0.844 |
Size of primary tumor |
T1-2 |
51.2±5 |
42.3±5.2 |
50.7±5.5 |
42.2±5.8 |
0.848 |
T3-4 |
47.9±8.3 |
35.2±8.8 |
55.1±9.5 |
47.2±10.9 |
0.174 |
Histology |
Squamous cell carcinoma |
57.9±5.6 |
51.6±5.8 |
59.1±6.3 |
56.6±6.5 |
0.44 |
Adenocarcinoma |
37±6.6 |
21±6.4 |
41.2±7.9 |
21±7.8 |
0.867 |
图 2 T3-4N1M0患者总的生存率(A)和无瘤生存率(B)
Fig 2 Overall survival rates and disease-free survival rates of patients with T3-4N1M0 disease
2.3 治疗失败原因分析 术后放疗组患者的胸内复发、锁骨上淋巴结转移、远处转移率分别为12.7%、13.4%和48.5%,单纯手术组为33.3%、11.7%与51.2%。术后放疗能明显减少胸内复发(P<0.01)。疗后失败原因的分析见表3。
3 讨论
关于根治术后放射治疗对NSCLC的疗效,文献已报道许多研究结果。目前一般认为对T1-2、N0的Ⅰ期患者给予术后放疗无益,反而产生一定的副作用,降低生存率[1,2]。对于N1、N2与T3-4的患者,尚无明确肯定的结论,回顾性分析发现术后放疗有效[3],但随机性研究未获得相似结果。部分研究报道,术后放疗可以减少局部复发,但术后生存率改善不明显或反而降低[1,4~6]。1998年英国剑桥报导了用Meta分析总结的9个单位共2128例随机化分组研究结果,认为术后放疗可以明显减少局部复发和延迟转移出现,但术后放疗者生存率下降7%,死亡危险性增加21%;术后放疗对Ⅰ、Ⅱ期患者无益,对Ⅲ期、N2患者疗效稍好[7]。该报道虽来自对较大病例数的分析,但由于是多中心的治疗结果,治疗时间、患者病期以及治疗方法和放射剂量等因素均难一致。我们的研究结果显示,术后放疗可以降低胸内复发,但对患者总的生存无明显改善,与国际一些文献报道的结果相似。我们也未发现术后放疗导致Ⅱ期患者总生存率降低。因此,我们认为综合有效化疗有望提高长期生存率。
表 3 两组治疗失败原因分析
Tab 3 Analysis of therapy failure in the two groups
Items |
No.of cases (%) |
Overall failure |
Loco-regional recurrence |
Supraclavicular lymph node metastasis |
Distant metastasis |
S alone |
S+R |
S alone |
S+R |
S alone |
S+R |
S alone |
S+R |
Histology |
Squamous cell carcinoma |
52(58.4) |
39(51.3) |
31.(34.8) |
12(16) |
9(8.7) |
8(10.5) |
37(41.6) |
27(35.5) |
Adenocarcinoma |
50(78.1) |
36(75) |
21(32.8) |
4(8.3) |
7(10) |
8(16.7) |
45(70.3) |
33(69) |
Size of primary tumor |
T1-2 |
73(62.4) |
56(58.2) |
36(30.8) |
11(11.3) |
12(10.3) |
13(13.2) |
55(47) |
46(47.4) |
T3-4 |
32(71) |
24(65) |
18(40) |
6(16) |
7(15.6) |
5(13.5) |
28(62) |
19(51) |
Lymph node status |
N1 |
69(58.5) |
36(50) |
37(31.4) |
5(6.8) |
12(10.2) |
7(9.6) |
51(43.2) |
30(41) |
N2 |
36(81.8) |
44(72) |
17(38.6) |
12(19.7) |
7(15.6) |
11(18) |
32(73) |
35(57.4) |
TNM stage |
Ⅱ |
47(57.3) |
26(50) |
24(29.3) |
4(7.7) |
7(8.5) |
5(9.6) |
32(39.2) |
20(38.5) |
Ⅲ |
58(72.5) |
54(66) |
30(37.5) |
13(15.6) |
12(15) |
13(15.8) |
51(63.8) |
45(55) |
postoperative radiation significantly decreased the loco-regional recurrence (P<0.05-0.001),but showed no effects on supraclavicular lymph node metastases and distant metastases. 另外我们发现,对T3-4患者、N1患者以及Ⅲ期患者,给予术后放疗后有提高生存率的趋势,在N2患者中两组疗效相似。从失败原因看,单纯手术组N2患者主要为远处转移(73%),而N1患者的远处转移占43.2%,局部复发占31.4%,说明术后放疗明显降低局部复发,对N1患者更显重要。Immerman等[8]也认为N1病变首次复发倾向为局部复发,术后放疗可能可以杀灭纵隔内残留下的亚临床病灶。因此,对T3-4N1M0患者给予术后放疗,可能因减少局部复发而获得一定的生存改善,但尚未达到统计学上的差别。可能与病例数少有关。
总之,术后放疗可减少局部复发,对总生存改善不明显,但对局部病变较晚(T3-4),淋巴结转移较早者(N1),可望得到治疗益处。
参考文献
1,Lafitte JJ,Ribet ME,Provost BM,et al.Post-irradiation for T2N0M0 non-small cell lung carcinoma: A prospective randomised study.Ann Thorac Surg,1996,62(3)∶830-834.
2,Van Houtte P,Rocmans P,Smets P.Postoperative radiation therapy in lung cancer: A controlled trial after resection of curative design.Int J Radiat Oncol Biol Phys,1980,6(8)∶983-986.
3,Lewin A,Lavin P,Malcolm A.Post resection radiation therapy of bronchogenic carcinoma.Int J Radiat Oncol Biol Phys,1981,7(9)∶1224.
4,Stephens Rj,Girling DJ,Bleehen NM,et al.The role of postoperative radiotherapy in non-small cell lung cancer: a multicentre randomised trial in patients with pathologically staged T1-2,N1-2,M0 disease.Br J Cancer,1996,74(4)∶632-639.
5,Lung Cancer Study Group.Effects of postoperative mediastinal radiation on completely resected stage Ⅱ and stage Ⅲ epidermoid cancer of the lung.N Engl J Med,1986,315(22)∶1377-1381.
6,Debevec M,Bitnec M,Vidmar S.Postoperative radiotherapy for radically resected N2 non-small cell lung cancer: randomised clinical study 1988-92.Lung Cancer,1996,14(1)∶1499-1507.
7,PORT Meta-analysis Trialists Group.Postoperative radiotherapy in non-small-cell lung cancer: systematic review and Meta-analysis of individual patient data from nine randomised controlled trial.Lancet,1998,352(9124)∶257-263.
8,Immerman SC,Vanecko RM,Fry WA,et al.Site of recurrence in patients with stage Ⅰ and Ⅱ carcinoma of the lung resected for cure.Ann Thorac Surg,1981,32(1)∶23-27.
收稿日期:2000-06-05
修回日期:2000-07-30