根治性切除ⅢA期-N2非小细胞肺癌的术后放疗
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摘要
第一部分:根治性切除ⅢA期-N2非小细胞肺癌的术后放疗
目的回顾性研究术后放疗在根治性切除ⅢA期-N2非小细胞肺癌治疗中的作用及影响生存预后的因素。方法2003年1月～2005年12月221例根治性切除术后病理分期为ⅢA期-N2的非小细胞肺癌患者,96例(43.4%)接受了术后放疗,全组共161例(72.9%)接受了辅助化疗。结果全组病例的中位生存时间和1、3、5年生存率分别为为37.9个月、85.5%、51.3%、32.7%。在术后放疗组中位生存时间、1、3、5年生存率分别为43.9个月、94.8%、59.1%、34.3%,在无术后放疗组分别为31.8个月、77.6%、45.4%、30.6%,差异具有统计学显著性(P=0.046),两组间局部区域无复发生存率、无远转生存率和无病生存率的差异均具有统计学显著性。术后放疗对于接受或未接受辅助化疗的病例均可改善生存率。术后采用联合放化疗组生存结果优于接受单一放疗/化疗组,而未接受任何辅助治疗的病例生存结果最差。亚组分析显示临床N2期、鳞癌、T3期和≥4枚阳性淋巴结的病例可从术后放疗中获得生存改善。非肿瘤死亡率在术后放疗组为5.3%,无术后放疗组为6.4%,差异无统计学显著性(p=0.493)。多因素分析显示临床N分期、阳性淋巴结数目百分比、有无术后放疗、有无术后化疗是影响ⅢA期-N2非小细胞肺癌生存的独立因素。结论术后放疗可以改善根治性切除后ⅢA期-N2非小细胞肺癌的生存结果。临床N2期、鳞癌、T3期和≥4枚阳性淋巴结的病例可从术后放疗中获得生存改善,临床N分期、阳性淋巴结数目百分比、术后放疗和术后化疗是影响ⅢA期-N2非小细胞肺癌预后的独立因素。
第二部分:非小细胞肺癌的术后放射治疗—三维适形放疗与常规放疗治疗结果比较
目的回顾性比较非小细胞肺癌术后三维适形放疗和常规放疗的疗效、失败模式及毒性反应。方法分析自2002年11月～2006年3月接受术后放疗的ⅠB-ⅢB非小细胞肺癌病例患者162例,其中86例采用三维适形放射治疗(Three-Dimensional Conformal Radiotherapy 3DCRT),76例采用常规放疗。3DCRT组和常规放疗组中位随访时间分别为29.4个月和33.8个月。结果3DCRT和常规放疗组两组间局部区域无复发生存率的差异具有显著性(x~2=5.458 P=0.019),两组间总生存率、无病生存率和无远转生存率的差异均不具显著性;总局部区域失败率3DCRT和常规放疗组分别为14.5%和33.3%,差异具有显著性(x~2=7.704 P=0.006),总远地转移率两组间的差异不具备显著性(x~2=0.015 P=0.904)。NCI CTC 2-3级放射性肺炎发生率3DCRT组显著低于常规放疗组(11.6%vs 23.7%x~2=4.102P=0.043)。结论术后放射治疗采用3DCRT技术与常规放疗技术比较能够提高局部控率,降低放疗相关肺毒性反应发生率。
PartⅠ:Effect of PORT for completely resceted stageⅢA-N2 non-small cell lung cancer
Objective To retrospectively analyze the role of postoperative radiotherapy(PORT) in patients with completely resected stageⅢA-N2 non-small cell lung cancer(NSCLC)and identify the potential prognostic factors.Methods From Jan 2003 to Dec 2005 221 patients with completely resected pathological stageⅢA-N2 NSCLC cancer was analyzed,96 cases received PORT.161 patients(72.9%) were treated with median 4 cycles of adjuvant chemotherapy.Results The median survival time(MST),1-,3- and 5-years overall survival rates(OS) was 43.9 months,94.8%、59.1%、34.3%for PORT group vesus 31.8 months,77.6%,45.4%,30.6%for group without PORT(P=0.046).The difference in the rates of loco-regional relapse-free survival(LRRFS),distant metastasis-free survival(DMFS) and disease-free survival(DFS) between the two groups both reached a statistically significance.Stratified analysis showed survival was improved in patients received PORT,both in the patients with chemotherapy(MST48.3 vs.33.1 months) and without(MST 38.3 vs.21.6 months). Patients received chemoradiotherapy got better survival outcome than patients received either chemotherapy or PORT,those patients without any adjuvant therapy had the worst survival outcome.Subgroups with clinical N2 stage,squamous cell carcinoma types, stage T3,no less than 4 lymph node involved could gain definite survival benefit from PORT.Intercurrent death rate was 5.3%in PORT group and 6.4%in group without PORT(P=0.493).In multivariable Cox proportional hazards models,percentage of involved lymph nodes,clinical N stage,PORT and adjuvant chemotherapy were independent prognostic factors.Conclusions PORT can improve survival in patients with completely resceted stageⅢA-N2 NSCLC.Subgroups with clinical N2 stage, squamous cell carcinoma type,stage T3,no less than 4 lymph node involved can gain definite survival benefit from PORT.clinical N stage,percentage of involved lymph nodes,postoperative radiotherapy and adjuvant chemotherapy were independent prognostic factors.
PartⅡ:Postoperative Radiotherapy for Non-Small Cell Lung Cancer: A Comparison of Three-Dimensional Conformal Radiotherapy with Conventional Radiotherapy
Objective To evaluate the survival outcome,pattern of failure and therapy-related side effect of postoperative Three-Dimensional Conformal Radiotherapy(3DCRT) and Conventional Radiotherapy in patients with resected non-small-cell lung cancer(NSCLC).Methods 162 patients with stageⅠB-ⅢB NSCLC received postoperative radiotherapy from Nov.2002 to Mar 2006 was restrospetcively analyzed.86 patients received 3DCRT,76 patients receieved conventional radiotherapy among the whole group.The median follow-up was 29.4 months in the 3DCRT group and 24 months in the conventional radiation group.Resulets There was statistically significant difference between 3DCRT group and conventional radiation group in terms of local-regional free survival(χ~2 =5.458 P= 0.019).No statistically significant difference was found in overall survival,disease-flee survival and distant metastasis-free survival between the two group.Statistically significant difference was found in local-regional failure rate between the 3DCRT group and conventional radiation group (14.5%vs 33.3%χ~2 =7.704 P=0.006),No statistically significant difference was found about the incidence of distant metastasis between the two group(χ~2 =0.015 P= 0.904). Pneumonitis for NCI CTC grade 2-3 occured in 10 patients(11.6%) in 3DCRT gourp and 18 patients(23.7%) in conventional radiation group.Incidence of radiation pneumonitis grade 2-3 was Statistically different:among the two group(χ~2= 4.102 P=0.043). Conclusions Postoperative 3DCRT for NSCLC provide a better local-regional control and lower incidence of radiation pneumonitis compared with conventional therapy.
目的回顾性研究术后放疗在根治性切除ⅢA期-N2非小细胞肺癌治疗中的作用及影响生存预后的因素。方法2003年1月～2005年12月221例根治性切除术后病理分期为ⅢA期-N2的非小细胞肺癌患者,96例(43.4%)接受了术后放疗,全组共161例(72.9%)接受了辅助化疗。结果全组病例的中位生存时间和1、3、5年生存率分别为为37.9个月、85.5%、51.3%、32.7%。在术后放疗组中位生存时间、1、3、5年生存率分别为43.9个月、94.8%、59.1%、34.3%,在无术后放疗组分别为31.8个月、77.6%、45.4%、30.6%,差异具有统计学显著性(P=0.046),两组间局部区域无复发生存率、无远转生存率和无病生存率的差异均具有统计学显著性。术后放疗对于接受或未接受辅助化疗的病例均可改善生存率。术后采用联合放化疗组生存结果优于接受单一放疗/化疗组,而未接受任何辅助治疗的病例生存结果最差。亚组分析显示临床N2期、鳞癌、T3期和≥4枚阳性淋巴结的病例可从术后放疗中获得生存改善。非肿瘤死亡率在术后放疗组为5.3%,无术后放疗组为6.4%,差异无统计学显著性(p=0.493)。多因素分析显示临床N分期、阳性淋巴结数目百分比、有无术后放疗、有无术后化疗是影响ⅢA期-N2非小细胞肺癌生存的独立因素。结论术后放疗可以改善根治性切除后ⅢA期-N2非小细胞肺癌的生存结果。临床N2期、鳞癌、T3期和≥4枚阳性淋巴结的病例可从术后放疗中获得生存改善,临床N分期、阳性淋巴结数目百分比、术后放疗和术后化疗是影响ⅢA期-N2非小细胞肺癌预后的独立因素。
第二部分:非小细胞肺癌的术后放射治疗—三维适形放疗与常规放疗治疗结果比较
目的回顾性比较非小细胞肺癌术后三维适形放疗和常规放疗的疗效、失败模式及毒性反应。方法分析自2002年11月～2006年3月接受术后放疗的ⅠB-ⅢB非小细胞肺癌病例患者162例,其中86例采用三维适形放射治疗(Three-Dimensional Conformal Radiotherapy 3DCRT),76例采用常规放疗。3DCRT组和常规放疗组中位随访时间分别为29.4个月和33.8个月。结果3DCRT和常规放疗组两组间局部区域无复发生存率的差异具有显著性(x~2=5.458 P=0.019),两组间总生存率、无病生存率和无远转生存率的差异均不具显著性;总局部区域失败率3DCRT和常规放疗组分别为14.5%和33.3%,差异具有显著性(x~2=7.704 P=0.006),总远地转移率两组间的差异不具备显著性(x~2=0.015 P=0.904)。NCI CTC 2-3级放射性肺炎发生率3DCRT组显著低于常规放疗组(11.6%vs 23.7%x~2=4.102P=0.043)。结论术后放射治疗采用3DCRT技术与常规放疗技术比较能够提高局部控率,降低放疗相关肺毒性反应发生率。
PartⅠ:Effect of PORT for completely resceted stageⅢA-N2 non-small cell lung cancer
Objective To retrospectively analyze the role of postoperative radiotherapy(PORT) in patients with completely resected stageⅢA-N2 non-small cell lung cancer(NSCLC)and identify the potential prognostic factors.Methods From Jan 2003 to Dec 2005 221 patients with completely resected pathological stageⅢA-N2 NSCLC cancer was analyzed,96 cases received PORT.161 patients(72.9%) were treated with median 4 cycles of adjuvant chemotherapy.Results The median survival time(MST),1-,3- and 5-years overall survival rates(OS) was 43.9 months,94.8%、59.1%、34.3%for PORT group vesus 31.8 months,77.6%,45.4%,30.6%for group without PORT(P=0.046).The difference in the rates of loco-regional relapse-free survival(LRRFS),distant metastasis-free survival(DMFS) and disease-free survival(DFS) between the two groups both reached a statistically significance.Stratified analysis showed survival was improved in patients received PORT,both in the patients with chemotherapy(MST48.3 vs.33.1 months) and without(MST 38.3 vs.21.6 months). Patients received chemoradiotherapy got better survival outcome than patients received either chemotherapy or PORT,those patients without any adjuvant therapy had the worst survival outcome.Subgroups with clinical N2 stage,squamous cell carcinoma types, stage T3,no less than 4 lymph node involved could gain definite survival benefit from PORT.Intercurrent death rate was 5.3%in PORT group and 6.4%in group without PORT(P=0.493).In multivariable Cox proportional hazards models,percentage of involved lymph nodes,clinical N stage,PORT and adjuvant chemotherapy were independent prognostic factors.Conclusions PORT can improve survival in patients with completely resceted stageⅢA-N2 NSCLC.Subgroups with clinical N2 stage, squamous cell carcinoma type,stage T3,no less than 4 lymph node involved can gain definite survival benefit from PORT.clinical N stage,percentage of involved lymph nodes,postoperative radiotherapy and adjuvant chemotherapy were independent prognostic factors.
PartⅡ:Postoperative Radiotherapy for Non-Small Cell Lung Cancer: A Comparison of Three-Dimensional Conformal Radiotherapy with Conventional Radiotherapy
Objective To evaluate the survival outcome,pattern of failure and therapy-related side effect of postoperative Three-Dimensional Conformal Radiotherapy(3DCRT) and Conventional Radiotherapy in patients with resected non-small-cell lung cancer(NSCLC).Methods 162 patients with stageⅠB-ⅢB NSCLC received postoperative radiotherapy from Nov.2002 to Mar 2006 was restrospetcively analyzed.86 patients received 3DCRT,76 patients receieved conventional radiotherapy among the whole group.The median follow-up was 29.4 months in the 3DCRT group and 24 months in the conventional radiation group.Resulets There was statistically significant difference between 3DCRT group and conventional radiation group in terms of local-regional free survival(χ~2 =5.458 P= 0.019).No statistically significant difference was found in overall survival,disease-flee survival and distant metastasis-free survival between the two group.Statistically significant difference was found in local-regional failure rate between the 3DCRT group and conventional radiation group (14.5%vs 33.3%χ~2 =7.704 P=0.006),No statistically significant difference was found about the incidence of distant metastasis between the two group(χ~2 =0.015 P= 0.904). Pneumonitis for NCI CTC grade 2-3 occured in 10 patients(11.6%) in 3DCRT gourp and 18 patients(23.7%) in conventional radiation group.Incidence of radiation pneumonitis grade 2-3 was Statistically different:among the two group(χ~2= 4.102 P=0.043). Conclusions Postoperative 3DCRT for NSCLC provide a better local-regional control and lower incidence of radiation pneumonitis compared with conventional therapy.
引文
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1.Vansteenkiste JF,De Leyn PR,Deneffe GJ,et al.Clinical prognostic factors in surgically treated stage ⅢA-N2 non-small cell lung cancer:analysis of the literature[J].Lung Cancer 1998;19:3-13.
2.Suzuki K,Nagai K,Yoshida J,et al.The prognosis of surgically resected N2 non-small cell lung cancer:the importance of clinical N status[J].J Thorac Cardiovasc Surg 1999;118:145-153.
3.Kim KJ,Ahn YC,Lim do H,et al.Analyses on prognostic factors following tri-modality therapy for stage Ilia non-small cell lung cancer[J].Lung Cancer 2007;55:329-336.
4.Casali C,Stefani A,Natali P,et al.Prognostic factors in surgically resected N2 non-small cell lung cancer:the importance of patterns of mediastinal lymph nodes metastases[J].Eur J Cardiothorac Surg 2005;28:33-38.
5.Martini N,Flehinger BJ.The role of surgery in N2 lung cancer[J].Surg Clin North Am 1987;67:1037-1049.
6.Andre F,Grunenwald D,Pignon JP,et al.Survival of patients with resected N2 non-small-cell lung cancer:evidence for a subclassification and implications[J].J Clin Oncol 2000;18:2981-2989.
7.Stephens RJ,Girling DJ,Bleehen NM,et al.The role of post-operative radiotherapy in non-small-cell lung cancer:a multicentre randomised trial in patients with pathologically staged T1-2,N1-2,M0 disease.Medical Research Council Lung Cancer Working Party[J].Br J Cancer 1996;74:632-639.
8.Effects of postoperative mediastinal radiation on completely resected stage Ⅱ and stage Ⅲ epidermoid cancer of the lung.The Lung Cancer Study Group[J],N Engl J Med 1986;315:1377-1381.
9.Mayer R,Smolle-Juettner FM,Szolar D,et al.Postoperative radiotherapy in radically resected non-small cell lung cancer[J].Chest 1997;112:954-959.
10.Feng QF,Wang M,Wang LJ,et al.A study of postoperative radiotherapy in patients with non-small-cell lung cancer:a randomized trial[J].Int J Radiat Oncol Biol Phys 2000;47:925-929.
11.Postoperative radiotherapy in non-small-cell lung cancer:systematic review and meta-analysis of individual patient data from nine randomised controlled trials.PORT Meta-analysis Trialists Group[J].Lancet 1998;352:257-263.
12.Lally BE,Zelterman D,Colasanto JM,et al.Postoperative radiotherapy for stage Ⅱ or Ⅲ non-small-cell lung cancer using the surveillance,epidemiology,and end results database[J]. J Clin Oncol 2006;24:2998-3006..
13.Douillard JY,Rosell R,De Lena M,et al.Impact of postoperative radiation therapy on survival in patients with complete resection and stage Ⅰ,Ⅱ,or ⅢA non-small-cell lung cancer treated with adjuvant chemotherapy:the adjuvant Navelbine International Trialist Association (ANITA) Randomized Trial[J].Int J Radiat Oncol Biol Phys 2008;72:695-701.
14.Inoue M,Sawabata N,Takeda S,et al.Results of surgical intervention for p-stage ⅢA(N2)non-small cell lung cancer:acceptable prognosis predicted by complete resection in patients with single N2 disease with primary tumor in the upper lobe[J].J Thorac Cardiovasc Surg 2004;127:1100-1106.
15.Saito M,Kato H.Prognostic factors in patients with pathological and N2 non-small cell lung cancer[J].Ann Thorac Cardiovasc Surg 2008;14:1-2.
16.Vansteenkiste JF,De Leyn PR,Deneffe GJ,et al.Survival and prognostic factors in resected N2 non-small cell lung cancer:a study of 140 cases.Leuven Lung Cancer Group[J].Ann Thorac Surg 1997;63:1441-1450.
17.Mountain CE Surgery for stage Ⅲa-N2 non-small cell lung cancer[J].Cancer 1994;73:2589-2598.
18.黄国俊,方德康,程贵余,等.非小细胞肺癌纵隔淋巴结转移(N2)的外科治疗选择[J].中华肿瘤杂志2006年:28:62-64.
19.Keller SM,Adak S,Wagner H,et al.A randomized trial of postoperative adjuvant therapy in patients with completely resected stage Ⅱ or ⅢA non-small-cell lung cancer.Eastern Cooperative Oncology Group[J].N Engl J Med 2000;343:1217-1222.
20.Goldstraw P,Mannam GC,Kaplan DK,et al.Surgical management of non-small-cell lung cancer with ipsilateral mediastinal node metastasis(N2 disease)[J].J Thorac Cardiovasc Surg 1994;107:19-27;discussion 27-18.
21.Ichinose Y,Kato H,Koike T,et al.Overall survival and local recurrence of 406 completely resected stage Ⅲa-N2 non-small cell lung cancer patients:questionnaire survey of the Japan Clinical Oncology Group to plan for clinical trials[J].Lung Cancer 2001;34:29-36.
22.Takenaka K,Ishikawa S,Yanagihara K,et al.Prognostic significance of reversion-inducing cysteine-rich protein with Kazal motifs expression in resected pathologic stage ⅢA N2non-small-cell lung cancer[J].Ann Surg Oncol 2005;12:817-824.
23.Pignon JP,Tribodet H,Scagliotti GV,et al.Lung Adjuvant Cisplatin Evaluation(LACE):A pooled analysis of five randomized clinical trials including 4,584 patients[A].2006 ASCO Annual Meeting Proceedings."7008.
24.Stewart LA,Burdett S,Tierney JF,et al.Surgery and adjuvant chemotherapy(CT) compared to surgery alone in non-small cell lung cancer(NSCLC):A meta-analysis using individual patient data(IPD)from randomized clinical trials(RCT)[A].2007.7552.
25.Hotta K,Matsuo K,Ueoka H,et al.Role of adjuvant chemotherapy in patients with resected non-small-cell lung cancer:reappraisal with a meta-analysis of randomized controlled trials[A].2004,Am Soc Clin Oncol.3860.
26.Pisters KMW,Evans WK,Azzoli CG,et al.Cancer Care Ontario and American Society of Clinical Oncology adjuvant chemotherapy and adjuvant radiation therapy for stages I-ⅢA resectable non small-cell lung cancer guideline.Vol 25:Am Soc Clin Oncol;2007.p.5506.
27.Ruckdeschel JC.Combined modality therapy of non-small cell lung cancer[J].Semin Oncol 1997;24:429-439.
28.Robinson LA,Wagner H,Jr.,Ruckdeschel JC.Treatment of stage IIIA non-small cell lung cancer[J].Chest 2003;123:202S-220S.
29.Spira A,Ettinger DS.Multidisciplinary management of lung cancer.Vol 350;2004.pp.379-392.
30.Machtay M,Lee JH,Shrager JB,et al.Risk of death from intercurrent disease is not excessively increased by modern postoperative radiotherapy for high-risk resected non-small-cell lung carcinoma[J].J Clin Oncol 2001;19:3912-3917.
31.Bonner J.The role of postoperative radiotherapy for patients with completely resected nonsmall cell lung carcinoma:Seeking to optimize local control and survival while minimizing toxicity[J].Cancer 1999;86:195-196.
32.Bekelman JE.Trends in the use of postoperative radiotherapy for resected non-small-cell lung cancer.[J].Int J Radiat Oncol Biol Phys 2006;66:492-499.
33.Uno T,Sumi M,Kihara A,et al.Postoperative radiotherapy for non-small-cell lung cancer:results of the 1999-2001 patterns of care study nationwide process survey in Japan[J].Lung Cancer 2007;56:357-362.
34.Douillard JY,Rosell R,De Lena M,et al.Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer(Adjuvant Navelbine International Trialist Association[ANITA]):a randomised controlled trial[J].Lancet Oncol 2006;7:719-727.
35.Bradley JD,Paulus R,Graham MV,et al.Phase Ⅱ trial of postoperative adjuvant paclitaxel/carboplatin and thoracic radiotherapy in resected stage Ⅱ and ⅢA non-small-cell lung cancer:promising long-term results of the Radiation Therapy Oncology Group-RTOG 9705[J].J Clin Oncol 2005;23:3480-3487.
36.Dautzenberg B,Arriagada R,Chammard AsB,et al.A Controlled Study of Postoperative Radiotherapy for Patients with Completely Resected Nonsmall Cell Lung Carcinoma[J].CANCER 1999;86:265-273.
37.Fang LC,Komaki R,Allen P,et al.Comparison of outcomes for patients with medically inoperable Stage Ⅰ non-small-cell lung cancer treated with two-dimensional vs.three-dimensional radiotherapy[J].Int J Radiat Oncol Biol Phys 2006;66:108-116.
38.梁军,冯勤付,张可,等.肺癌三维适形放疗与常规放疗剂量学优势的比较[J].临床肿瘤学杂志2006:11:814-817.
39.Wilson EM,Joy Williams F,Lyn BE,et al.Comparison of two dimensional and three dimensional radiotherapy treatment planning in locally advanced non-small cell lung cancer treated with continuous hyperfractionated accelerated radiotherapy weekend less[J].Radiother Oncol 2005;74:307-3114.
40.Bradley J,Graham MV,Winter K,et al.Toxicity and outcome results of RTOG 9311:a phase Ⅰ-Ⅱ dose-escalation study using three-dimensional conformal radiotherapy in patients with inoperable non-small-cell lung carcinoma[J].Int J Radiat Oncol Biol Phys 2005;61:318-328.
1.Effects of postoperative mediastinal radiation on completely resected stage Ⅱ and stage Ⅲepidermoid cancer of the lung.The Lung Cancer Study Group.[J].N Engl J Med 1986;315:1377-1381.
2.Stephens R,Girling,DJ,Bleehen,NM.The role of post-operative radiotherapy in non-small-cell lung cancer:A multicentre randomised trial in patients with pathologically staged T1-2,N1-2,M0 disease.Medical Research Council Lung Cancer Working Party.[J].Br J Cancer 1996;74:632-639.
3.Dautzenberg B,Arfiagada R,Chammard AsB,et al.A Controlled Study of Postoperative Radiotherapy for Patients with Completely Resected Nonsmall Cell Lung Carcinoma[J].CANCER 1999;86:265-273.
4.Postoperative radiotherapy in non-small-cell lung cancer:systematic review and meta-analysis of individual patient data from nine randomised controlled trials.PORT Meta-analysis Trialists Group.[J].Lancet Oncol 1998;352:257-263.
5.Machtay M,Lee JH,Shrager JB,et al.Risk of Death From Intercurrent Disease Is Not Excessively Increased by Modem Postoperative Radiotherapy for High-Risk Resected Non-Small-Cell Lung Carcinoma[J].Journal of Clinical Oncology 2001;19:3912-3917.
6.Douillard JY,Rosell R,De Lena M,et al.Impact of postoperative radiation therapy on survival in patients with complete resection and stage Ⅰ,Ⅱ,or ⅢA non-small-cell lung cancer treated with adjuvant chemotherapy:the adjuvant Navelbine International Trialist Association (ANITA) Randomized Trial[J].Int J Radiat Oncol Biol Phys 2008;72:695-701.
7.Unoa T,Sumib M,Kiharac A,et al.Postoperative radiotherapy for non-small-cell lung cancer:Results of the 1999-2001 patterns of care study nationwide process survey in Japan[J].Lung Cancer 2007;56:357-362.
8.Bekelman JE.Trends in the use of postoperative radiotherapy for resected non-small-cell lung cancer.[J].Int J Radiat Oncol Biol Phys 2006;66:492-499.
9.Bonner J.The role of postoperative radiotherapy for patients with completely resected nonsmall cell lung carcinoma:Seeking to optimize local control and survival while minimizing toxicity[J].Cancer 1999;86:195-196.
10.Lally BE,Zelterman D,Colasanto JM.Postoperative Radiotherapy for Stage Ⅱ or ⅢNon-Small-Cell Lung Cancer Using the Surveillance,Epidemiology,and End Results Database[J].J Clin Oncol 2006;24:2998-3006.
11.中国抗癌协会肺癌专业委员会,2007中国肺癌临床指南.[J].人民卫生出版社2007:106-107.
12.Pignon JP,Tribodet H,Scagliotti GV,et al.Lung Adjuvant Cisplatin Evaluation(LACE):A pooled analysis of five randomized clinical trials including 4,584 patients.Vol 24;2006.p.7008.
13.Stewart LA,Burdett S,Tierney JF,et al.Surgery and adjuvant chemotherapy(CT) compared to surgery alone in non-small cell lung cancer(NSCLC):A meta-analysis using individual patient data(IPD) from randomized clinical trials(RCT).Vol 25;2007.p.7552.
14.Pisters KM,Evans WK,Azzoli CG,et al.Cancer Care Ontario and American Society of Clinical Oncology adjuvant chemotherapy and adjuvant radiation therapy for stages Ⅰ-ⅢA resectable non small-cell lung cancer guideline[J].J Clin Oncol 2007;25:5506-5518.
15.Hotta K,Matsuo K,Ueoka H,et al.Role of adjuvant chemotherapy in patients with resected non-small-cell lung cancer:reappraisal with a meta-analysis of randomized controlled trials[J].J Ctin Oncol 2004;22:3860-3867.
16.Wilsona EM,Williamsb FJ,Lyna BE,et al.Comparison of two dimensional and three dimensional radiotherapy treatment planning in locally advanced non-small cell lung cancer treated with continuous hyperfractionated accelerated radiotherapy weekend less[J].Radiotherapy and Oncology 2005;74:307-314.
17.Bradley J,Graham M,Winter K,et al.Toxicity and outcome results of RTOG 9311:a phase Ⅰ-Ⅱ dose - escalation study using three-dimensional conformal radiotherapy in patientswith inoperable non - small cell lung carcinoma[J].Int J RadiatOncol Phys 2005;61318-328.
18.梁军,冯勤付,张可,等.肺癌三维适形放疗与常规放疗剂量学优势的比较[J].临床肿瘤学杂志2006:11:814-817.
19.Fang LC,Komaki R,Allen P,et al.Comparison of outcomes for patients with medically inoperable Stage Ⅰ non-small-cell lung cancer treated with two-dimensional vs.three-dimensional radiotherapy[J].Int J Radiat Oncol Biol Phys 2006;66:108-116.
20.Zhu G,Lin Y,Z.Liao,et al.Comparison of Outcomes in Patients with Pathological Stage Ⅰ-ⅢB Non-Small Cell Lung Cancer Treated with Postoperative Two- or Three-Dimensional Conformal Radiotherapy[J].Proceedings of the 47th Annual ASTRO Meeting S395.
21.Lin Y,Liao Z,Komaki R,et al.Evaluation of conventional radiotherapy vs.conformal radiotherapy in the treatment of non-small-cell lung cancer after surgical resection[J].Chinese-German Journal of Clinical Oncology 2007;6:514-518.
22.Feng QF,Wang M,Wang LJ,et al.A study of postoperative radiotherapy in patients with non-small-cell lung cancer:a randomized trial[J].Int J Radiat Oncol Biol Phys 2000;47:925-929.
2.Suzuki K,Nagai K,Yoshida J,et al.The prognosis of surgically resected N2 non-small cell lung cancer:the importance of clinical N status[J].J Thorac Cardiovasc Surg 1999;118:145-153.
3.Kim KJ,Ann YC,Lim do H,et al.Analyses on prognostic factors following tri-modality therapy for stage Ilia non-small cell lung cancer[J].Lung Cancer 2007;55:329-336.
4.Casali C,Stefani A,Natali P,et al.Prognostic factors in surgically resected N2 non-small cell lung cancer:the importance of patterns of mediastinal lymph nodes metastases[J].Eur J Cardiothorac Surg 2005;28:33-38.
5.Martini N,Flehinger BJ.The role of surgery in N2 lung cancer[J].Surg Clin North Am 1987;67:1037-1049.
6.Andre F,Grunenwald D,Pignon JP,et al.Survival of patients with resected N2 non-small-cell lung cancer:evidence for a subclassification and implications[J].J Clin Oncol 2000;18:2981-2989.
7.Effects of postoperative mediastinal radiation on completely resected stage Ⅱ and stage Ⅲ epidermoid cancer of the lung.The Lung Cancer Study Group[J].N Engl J Med 1986;315:1377-1381.
8.Stephens RJ,Girling DJ,Bleehen NM,et al.The role of post-operative radiotherapy in non-small-cell lung cancer:a multicentre randomised trial in patients with pathologically staged Tl-2,Nl-2,MO disease.Medical Research Council Lung Cancer Working Party.Vol 74;1996.p.632.
9.Mayer R,Smolle-Juettner FM,Szolar D,et al.Postoperative radiotherapy in radically resected non-small cell lung cancer[J].Chest 1997;112:954-959.
10.Feng QF,Wang M,Wang LJ,et al.A study of postoperative radiotherapy in patients with non-small-cell lung cancer:a randomized trial[J].Int J Radiat Oncol Biol Phys 2000;47:925-929.
11.Postoperative radiotherapy in non-small-cell lung cancer:systematic review and meta-analysis of individual patient data from nine randomised controlled trials.PORT Meta-analysis Trialists Group[J].Lancet 1998;352:257-263.
12.Lally BE,Zeltennan D,Colasanto JM,et al.Postoperative radiotherapy for stage Ⅱ or Ⅲ non-small-cell lung cancer using the surveillance,epidemiology,and end results database[J].J Clin Oncol 2006;24:2998-3006.
13.Douillard JY,Rosell R,De Lena M,et al.Impact of postoperative radiation therapy on survival in patients with complete resection and stage Ⅰ,Ⅱ,or ⅢA non-small-cell lung cancer treated with adjuvant chemotherapy:the adjuvant Navelbine International Trialist Association (ANITA) Randomized Trial[J].Int J Radiat Oncol Biol Phys 2008;72:695-701.
14.Inoue M,Sawabata N,Takeda S,et al.Results of surgical intervention for p-stage ⅢA(N2)non-small cell lung cancer:acceptable prognosis predicted by complete resection in patients with single N2 disease with primary tumor in the upper lobe[J].J Thorac Cardiovasc Surg 2004;127:1100-1106.
15.Saito M,Kato H.Prognostic factors in patients with pathological and N2 non-small cell lung cancer[J].Ann Thorac Cardiovasc Surg 2008;14:1-2.
16.Vansteenkiste JF,De Leyn PR,Deneffe GJ,et al.Survival and prognostic factors in resected N2 non-small cell lung cancer:a study of 140 cases.Leuven Lung Cancer Group[J].Ann Thorac Surg 1997;63:1441-1450.
17.Mountain CF.Surgery for stage Ⅲa-N2 non-small cell lung cancer[J].Cancer 1994;73:2589-2598.
18.黄国俊,方德康,程贵余,等.非小细胞肺癌纵隔淋巴结转移(N2)的外科治疗选择[J].中华肿瘤杂志 2006年;28:62-64.
19.Keller SM,Adak S,Wagner H,et al.A randomized trial of postoperative adjuvant therapy in patients with completely resected stage Ⅱ or ⅢA non-small-cell lung cancer.Eastern Cooperative Oncology Group[J].N Engl J Med 2000;343:1217-1222.
20.Goldstraw P,Mannam GC,Kaplan DK,et al.Surgical management of non-small-cell lung cancer with ipsilateral mediastinal node metastasis(N2 disease)[J].J Thorac Cardiovasc Surg 1994;107:19-27;discussion 27-18.
21.Grunenwald D,Le Chevalier T.Re:Stage ⅢA category of non-small-cell lung cancer:a new proposal[J].J Natl Cancer Inst 1997;89:88-89.
22.Ruckdeschel JC.Combined modality therapy of non-small cell lung cancer[J].Semin Oncol 1997;24:429-439.
23.Ichinose Y,Kato H,Koike T,et al.Overall survival and local recurrence of 406 completely resected stage Ⅲa-N2 non-small cell lung cancer patients:questionnaire survey of the Japan Clinical Oncology Group to plan for clinical trials[J].Lung Cancer 2001;34:29-36.
24.Takenaka K,Ishikawa S,Yanagihara K,et al.Prognostic significance of reversion-inducing cysteine-rich protein with Kazal motifs expression in resected pathologic stage ⅢA N2non-small-cell lung cancer[J].Ann Surg Oncol 2005;12:817-824.
25.Robinson LA,Wagner H,Jr.,Ruckdeschel JC.Treatment of stage ⅢA non-small cell lung cancer[J].Chest 2003;123:202S-220S.
26.Asamura H,Nakayama H,Kondo H,et al.Lobe-specific extent of systematic lymph node dissection for non-small cell lung carcinomas according to a retrospective study of metastasis and prognosis[J].J Thorac Cardiovasc Surg 1999;117:1102-1111.
27.Spira A,Ettinger DS.Multidisciplinary management of lung cancer.Vol 350;2004.pp.379-392.
28.Dautzenberg B,Arriagada R,Chammard AsB,et al.A Controlled Study of Postoperative Radiotherapy for Patients with Completely Resected Nonsmall Cell Lung Carcinoma[J].CANCER 1999;86:265-273.
29.Machtay M,Lee JH,Shrager JB,et al.Risk of death from intercurrent disease is not excessively increased by modern postoperative radiotherapy for high-risk resected non-small-cell lung carcinoma[J].J Clin Oncol 2001;19:3912-3917.
30.Bonner J.The role of postoperative radiotherapy for patients with completely resected nonsmall cell lung carcinoma:Seeking to optimize local control and survival while minimizing toxicity[J].Cancer 1999;86:195-196.
31.Unoa T,Sumib M,Kiharac A,et al.Postoperative radiotherapy for non-small-cell lung cancer:Results of the 1999—2001 patterns of care study nationwide process survey in Japan[J].Lung Cancer 2007;56:357-362.
32.Bekelman JE,Rosenzweig KE,Bach PB,et al.Trends in the use of postoperative radiotherapy for resected non-small-cell lung cancer[J].Int J Radiat Oncol Biol Phys 2006;66:492-499.
33.Uno T,Sumi M,Kihara A,et al.Postoperative radiotherapy for non-small-cell lung cancer:results of the 1999-2001 patterns of care study nationwide process survey in Japan[J].Lung Cancer 2007;56:357-362.
34.Douillard JY,Rosell R,De Lena M,et al.Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-ⅢA non-small-cell lung cancer(Adjuvant Navelbine International Trialist Association[ANITA]):a randomised controlled trial[J].Lancet Oncol 2006;7:719-727.
35.Bradley JD,Paulus R,Graham MV,et al.Phase Ⅱ trial of postoperative adjuvant paclitaxel/carboplatin and thoracic radiotherapy in resected stage Ⅱ and ⅢA non-small-cell lung cancer:promising long-term results of the Radiation Therapy Oncology Group-RTOG 9705[J].J Clin Oncol 2005;23:3480-3487.
36.Pignon JP,Tribodet H,Scagliotti GV,et al.Lung Adjuvant Cisplatin Evaluation(LACE):A pooled analysis of five randomized clinical trials including 4,584 patients.Vol 24;2006.p. 7008.
37.Stewart LA,Burdett S,Tierney JF,et al.Surgery and adjuvant chemotherapy(CT) compared to surgery alone in non-small cell lung cancer(NSCLC):A meta-analysis using individual patient data(IPD) from randomized clinical trials(RCT).Vol 25;2007.p.7552.
38.Pisters KM,Evans WK,Azzoli CG,et al.Cancer Care Ontario and American Society of Clinical Oncology adjuvant chemotherapy and adjuvant radiation therapy for stages Ⅰ-ⅢA resectable non small-cell lung cancer guideline[J].J Clin Oncol 2007;25:5506-5518.
39.Hotta K,Matsuo K,Ueoka H,et al.Role of adjuvant chemotherapy in patients with resected non-small-cell lung cancer:reappraisal with a recta-analysis of randomized controlled trials[J].J Clin Oncol 2004;22:3860-3867.
40.Fang LC,Komaki R,Allen P,et al.Comparison of outcomes for patients with medically inoperable Stage Ⅰ non-small-cell lung cancer treated with two-dimensional vs.three-dimensional radiotherapy[J].Int J Radiat Oncol Biol Phys 2006;66:108-116.
41.梁军,冯勤付,可张,等.肺癌三维适形放疗与常规放疗剂量学优势的比较[J].临床肿瘤学杂志2006:11:814-817.
42.Wilson EM,Joy Williams F,Lyn BE,et al.Comparison of two dimensional and three dimensional radiotherapy treatment planning in locally advanced non-small cell lung cancer treated with continuous hyperfractionated accelerated radiotherapy weekend less[J].Radiother Oncol 2005;74:307-314.
43.Bradley J,Graham MV,Winter K,et al.Toxicity and outcome results of RTOG 9311:a phase Ⅰ-Ⅱ dose-escalation study using three-dimensional conformal radiotherapy in patients with inoperable non-small-cell lung carcinoma[J].Int J Radiat Oncol Biol Phys 2005;61:318-328.
44.Le Pechoux C,Dunant A,Pignon JP,et al.Need for a new trial to evaluate adjuvant postoperative radiotherapy in non-small-cell lung cancer patients with N2 mediastinal involvement[J].J Clin Oncol 2007;25:e10-11.
45.Lin Y,Liao Z,Komaki R,et al.Evaluation of conventional radiotherapy vs.conformal radiotherapy in the treatment of non-small-cell lung cancer after surgical resection[J].Chinese-German Journal of Clinical Oncology 2007;6:514-518.
46.Zhu G,Lin Y,Z.Liao,et al.Comparison of Outcomes in Patients with Pathological Stage Ⅰ-ⅢB Non-Small Cell Lung Cancer Treated with Postoperative Two- or Three-Dimensional Confonnal Radiotherapy[J].Proceedings of the 47th Annual ASTRO Meeting S395.
1.Vansteenkiste JF,De Leyn PR,Deneffe GJ,et al.Clinical prognostic factors in surgically treated stage ⅢA-N2 non-small cell lung cancer:analysis of the literature[J].Lung Cancer 1998;19:3-13.
2.Suzuki K,Nagai K,Yoshida J,et al.The prognosis of surgically resected N2 non-small cell lung cancer:the importance of clinical N status[J].J Thorac Cardiovasc Surg 1999;118:145-153.
3.Kim KJ,Ahn YC,Lim do H,et al.Analyses on prognostic factors following tri-modality therapy for stage Ilia non-small cell lung cancer[J].Lung Cancer 2007;55:329-336.
4.Casali C,Stefani A,Natali P,et al.Prognostic factors in surgically resected N2 non-small cell lung cancer:the importance of patterns of mediastinal lymph nodes metastases[J].Eur J Cardiothorac Surg 2005;28:33-38.
5.Martini N,Flehinger BJ.The role of surgery in N2 lung cancer[J].Surg Clin North Am 1987;67:1037-1049.
6.Andre F,Grunenwald D,Pignon JP,et al.Survival of patients with resected N2 non-small-cell lung cancer:evidence for a subclassification and implications[J].J Clin Oncol 2000;18:2981-2989.
7.Stephens RJ,Girling DJ,Bleehen NM,et al.The role of post-operative radiotherapy in non-small-cell lung cancer:a multicentre randomised trial in patients with pathologically staged T1-2,N1-2,M0 disease.Medical Research Council Lung Cancer Working Party[J].Br J Cancer 1996;74:632-639.
8.Effects of postoperative mediastinal radiation on completely resected stage Ⅱ and stage Ⅲ epidermoid cancer of the lung.The Lung Cancer Study Group[J],N Engl J Med 1986;315:1377-1381.
9.Mayer R,Smolle-Juettner FM,Szolar D,et al.Postoperative radiotherapy in radically resected non-small cell lung cancer[J].Chest 1997;112:954-959.
10.Feng QF,Wang M,Wang LJ,et al.A study of postoperative radiotherapy in patients with non-small-cell lung cancer:a randomized trial[J].Int J Radiat Oncol Biol Phys 2000;47:925-929.
11.Postoperative radiotherapy in non-small-cell lung cancer:systematic review and meta-analysis of individual patient data from nine randomised controlled trials.PORT Meta-analysis Trialists Group[J].Lancet 1998;352:257-263.
12.Lally BE,Zelterman D,Colasanto JM,et al.Postoperative radiotherapy for stage Ⅱ or Ⅲ non-small-cell lung cancer using the surveillance,epidemiology,and end results database[J]. J Clin Oncol 2006;24:2998-3006..
13.Douillard JY,Rosell R,De Lena M,et al.Impact of postoperative radiation therapy on survival in patients with complete resection and stage Ⅰ,Ⅱ,or ⅢA non-small-cell lung cancer treated with adjuvant chemotherapy:the adjuvant Navelbine International Trialist Association (ANITA) Randomized Trial[J].Int J Radiat Oncol Biol Phys 2008;72:695-701.
14.Inoue M,Sawabata N,Takeda S,et al.Results of surgical intervention for p-stage ⅢA(N2)non-small cell lung cancer:acceptable prognosis predicted by complete resection in patients with single N2 disease with primary tumor in the upper lobe[J].J Thorac Cardiovasc Surg 2004;127:1100-1106.
15.Saito M,Kato H.Prognostic factors in patients with pathological and N2 non-small cell lung cancer[J].Ann Thorac Cardiovasc Surg 2008;14:1-2.
16.Vansteenkiste JF,De Leyn PR,Deneffe GJ,et al.Survival and prognostic factors in resected N2 non-small cell lung cancer:a study of 140 cases.Leuven Lung Cancer Group[J].Ann Thorac Surg 1997;63:1441-1450.
17.Mountain CE Surgery for stage Ⅲa-N2 non-small cell lung cancer[J].Cancer 1994;73:2589-2598.
18.黄国俊,方德康,程贵余,等.非小细胞肺癌纵隔淋巴结转移(N2)的外科治疗选择[J].中华肿瘤杂志2006年:28:62-64.
19.Keller SM,Adak S,Wagner H,et al.A randomized trial of postoperative adjuvant therapy in patients with completely resected stage Ⅱ or ⅢA non-small-cell lung cancer.Eastern Cooperative Oncology Group[J].N Engl J Med 2000;343:1217-1222.
20.Goldstraw P,Mannam GC,Kaplan DK,et al.Surgical management of non-small-cell lung cancer with ipsilateral mediastinal node metastasis(N2 disease)[J].J Thorac Cardiovasc Surg 1994;107:19-27;discussion 27-18.
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