外科治療ⅢA （N2）期非小細胞肺癌的爭議與共識_《中國胸心血管外科臨床雜志》

作者：

檀振波 , 國建飛 , 陳龍奇

1.邢臺市人民醫院　胸外科，河北邢臺　054031;;
2.四川大學華西醫院　胸外科，成都　610041;

關鍵詞：

非小細胞肺癌　N2期　外科手術　誘導化療　聯合放化療

DOI：

10.7507/1007-4848.20130177

視頻：

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ⅢA （N2）期非小細胞肺癌（non-small cell lung cancer ，NSCLC）治療方法的選擇一直存在爭議。單純外科手術治療效果差，誘導化療＋手術可明顯提高療效，已成為常用的治療模式。隨機研究表明，聯合放化療可獲得與外科手術相近的治療效果，而部分患者聯合外科手術可獲得明顯好的遠期生存率。低級別N2、誘導治療有效、縱隔淋巴結降級、采取肺葉切除能達到完全性切除的患者，是良好的外科手術適應證。臨床應根據不同的N2狀況，選擇合理的治療方法。巨塊狀、融合固定的N2患者應行根治性放化療；單部位、非巨塊、可手術切除的N2患者可采用包括手術在內的綜合治療；而對多部位N2患者應開展隨機的臨床研究，進一步確定可能從外科手術中獲益的N2患者亞組。

引用本文： 檀振波,國建飛,陳龍奇. 外科治療ⅢA （N2）期非小細胞肺癌的爭議與共識. 中國胸心血管外科臨床雜志, 2013, 20(5): 577-582. doi: 10.7507/1007-4848.20130177 復制

1.	Martini N， Flehinger BJ， Zaman MB， et al. Prospective study of 445 lung carcinomas with mediastinal lymph node metastases. J Thorac Cardiovasc Surg， 1980 ， 80 （3）：390-399.
2.	Cybulsky IJ， Lanza LA， Ryan MB， et al. Prognostic significance of computed tomography in resected N2 lung cancer. Ann Thorac Surg， 1992 ， 54 （3）：533-537.
3.	Pearson FG， DeLarue NC， Ilves R， et al. Significance of positive superior mediastinal nodes identified at mediastinoscopy in patients with resectable cancer of the lung. J Thorac Cardiovasc Surg， 1982， 83 （1）：1-11.
4.	Perez CA， Pajak TF， Rubin P， et al. Long-term observations of the patterns of failure in patients with unresectable non-oat cell carcinomaof the lung treated with definitive radiotherapy. Report by the RadiationTherapy Oncology Group. Cancer， 1987， 59 （11）：1874-1881.
5.	Vansteenkiste J， De Leyn P， Deneffe G， et al. Present status of induction treatment in stage ⅢA-N2 non-small cell lung cancer：a review.Eur J Cardiothorac Surg， 1998， 13 （1）：1-12.
6.	Pass HI， Pogrebniak HW， Steinberg SM， et al. Randomized trial of neoadjuvant therapy for lung cancer：interim analysis. Ann Thorac Surg， 1992， 53 （6）：992-998.
7.	Rosell R， Gómez-Codina J， Camps C， et al. A randomized trial comparing preoperative chemotherapy plus surgery with surgery alone in patients with non-small-cell lung cancer. N Engl J Med， 1994， 330 （3）：153-158.
8.	Roth JA， Fossella F， Komaki R， et al. A randomized trial comparingperioperative chemotherapy and surgery with surgery alone in resectablestage ⅢA non-small-cell lung cancer. J Natl Cancer Inst， 1994， 86 （9）：673-680.
9.	Roth JA， Atkinson EN， Fossella F， et al. Long-term follow-up of patients enrolled in a randomized trial comparing perioperative chemotherapy and surgery with surgery alone in resectable stage ⅢA non-small-cell lung cancer. Lung Cancer， 1998， 21 （1）：1-6.
10.	Depierre A， Milleron B， Moro D， et al. Phase Ⅲ trial of neo-adjuvantchemotherapy in resectable stage Ⅰ （except T1N0）， II and Ⅲa non-smallcell lung cancer：The French experience. J Clin Oncol， 2002 ， 20 （1）：247-253.
11.	Nagai K， Tsuchiya R， Mori T， et al. A randomized trial comparing induction chemotherapy followed by surgery with surgery alone for patients with stage ⅢA N2 non-small cell lung cancer （JCOG 9209） . J Thorac Cardiovasc Surg， 2003， 125 （2）：254-260.
12.	Pisters KM， Vallières E， Crowley JJ， et al. Surgery with or without preoperative paclitaxel and carboplatin in early-stage non-small-cell lung cancer：Southwest Oncology Group Trial S9900， an intergroup， randomized， phase Ⅲ trial. J Clin Oncol， 2010， 28 （11）：1843-1849.
13.	Scagliotti GV， Pastorino U， Vansteenkiste JF， et al. Randomized phase Ⅲ study of surgery alone or surgery plus preoperative cisplatin and gemcitabine in stages ⅠB to ⅢA non-small-cell lung cancer. J ClinOncol， 2012 ， 30 （2）：172-178.
14.	Dillman RO， Herndon J， Seagren SL， et al. Improved survival in stage Ⅲ non-small-cell lung cancer：seven-year follow-up of cancer and leukemia group B （CALGB） 8433 trial. J Natl Cancer Inst， 1996， 88 （17）：1210-1215.
15.	Le Chevalier T， Arriagada R， Quoix E， et al. Radiotherapy alone versus combined chemotherapy and radiotherapy in nonresectable non-small-cell lung cancer：first analysis of a randomized trial in 353 patients. J Natl Cancer Inst， 1991， 83 （6）：417-423.
16.	Sause W， Kolesar P， Taylor SIV， et al. Final results of phase Ⅲtrial in regionally advanced unresectable non-small cell lung cancer：Radiation therapy oncology group， eastern cooperative oncology group，and southwest oncology group. Chest， 2000， 117 （2）：358-364.
17.	Johnstone DW， Byhardt RW， Ettinger D， et al. Phase Ⅲ study comp-aring chemotherapy and radiotherapy with preoperative chemotherapy and surgical resection in patients with non-small-cell lung Cancer with spread to mediastinal lymph nodes （N2）；final report of RTOG 89-01. Radiation therapy oncology group. Int J Radiat Oncol Biol Phys， 2002， 54 （2）：365-369.
18.	Taylor NA， Liao ZX， Cox JD， et al. Equivalent outcome of patients with clinical stage ⅢA non-small-cell lung cancer treated with concurrent chemoradiation compared with induction chemotherapy followed by surgical resection. Int J Radiat Oncol Biol Phys， 2004， 58 （1）：204-212.
19.	Van Meerbeeck JP， Van Schil PE， Senan S. Reply：randomized controlled trial of resection versus radiotherapy after induction chemotherapy in stage ⅢA-N2 non-small cell lung cancer. J Natl Cancer Inst，2007， 2 （12）：1138-1139.
20.	Albain KS， Swann RS， Rusch VW， et al. Radiotherapy plus chemotherapy with or without surgical resection for stage Ⅲ non-small-cell lung cancer：a phase Ⅲ randomised controlled trial. Lancet， 2009， 374 （9687）：379-386.
21.	Bosch-Barrera J， García-Franco C， Guillén-Grima F， et al. The multimodal management of locally advanced N2 non-small cell lung cancer：is there a role for surgical resection ? A single institution's experience. Clin Transl Oncol， 2012， 14 （11）：835-841.
22.	Ratto GB， Costa R， Maineri P， et al. Is there a subset of patients with preoperatively diagnosed N2 non-small cell lung cancer who might benefit from surgical resection ? J Thorac Cardiovasc Surg， 2009 ， 138 （4）：849-858.
23.	Funakoshi Y， Takeuchi Y， Kusumoto H， et al. Which subgroup of patients with pathologic N2 non-small cell lung cancer benefit from surgery ? J Cancer Res Clin Oncol， 2012， 138 （6）：1027-1033.
24.	Sakao Y， Okumura S， Mun M， et al. Prognostic heterogeneity in multilevel N2 non-small cell lung cancer patients：importance of lymphadenopathy and occult intrapulmonary metastases. Ann Thorac Surg， 2010， 89 （4）：1060-1063.
25.	Lorent N， De Leyn P， Lievens Y， et al. Long-term survival of surgically staged ⅢA-N2 non-small-cell lung cancer treated with surgical combined modality approach：analysis of a 7-year prospective experience. Ann Oncol， 2004， 15 （11）：1645-1653.
26.	Stefani A， Alifano M， Bobbio A， et al. Which patients should be operated on after induction chemotherapy for N2 non-small cell lung cancer ? Analysis of a 7-year experience in 175 patients. J Thorac Cardiovasc Surg， 2010， 140 （2）：356-363.
27.	Lococo F， Cesario A， Margaritora S， et al. Long-term results in patients with pathological complete response after induction radiochemotherapy followed by surgery for locally advanced non-small-celllung cancer. Eur J Cardiothorac Surg， 2013， 43 （3）：e71-e81.
28.	Bueno R， Richards WG， Swanson SJ， et al. Nodal stage after induc-tion therapy for stage ⅢA lung cancer determines patient survival. AnnThorac Surg， 2000， 70 （6）：1826-1831.
29.	Decaluwé H， De Leyn P， Vansteenkiste J， et al. Surgical multimodality treatment for baseline resectable stage ⅢA-N2 non-small cell lungcancer. Degree of mediastinal lymph node involvement and impact on survival. Eur J Cardiothorac Surg， 2009 ， 36 （3）：433-439.
30.	Sawabata N， Keller SM， Matsumura A， et al. The impact of residualmulti-level N2 disease after induction therapy for non-small cell lung cancer. Lung Cancer， 2003， 42 （1）：69-77.
31.	Steger V， Walker T， Mustafi M， et al. Surgery on unfavourable persistent N2/N3 non-small-cell lung cancer after trimodal therapy：do the results justify the risk ? Interact Cardiovasc Thorac Surg， 2012 ， 15 （6）：948-953.
32.	Katakami N， Tada H， Mitsudomi T， et al. A phase 3 study of induction treatment with concurrent chemoradiotherapy versus chemotherapybefore surgery in patients with pathologically confirmed N2 stage ⅢA nonsmall cell lung cancer （WJTOG9903） . Cancer， 2012， 118 （24）：6126-6135.
33.	Koshy M， Fedewa SA， Malik R， et al. Improved survival associated with neoadjuvant chemoradiation in patients with clinical stage ⅢA （N2）non-small-cell lung cancer. J Thorac Oncol， 2013， 8 （7）：915-922.
34.	National Institute for Health and Clinical Excellence （NICE）. The Diagnosis and Treatment of Lung Cancer （Update）：Full Guideline. London：National Collaborating Centre for Cancer， 2011. 59-63.
35.	Lim E， Baldwin D， Beckles M， et al. Guidelines on the radical management of patients with lung cancer：British Thoracic Society and the Society for Cardiothoracic surgery in Great Britain and Ireland.Thorax ， 2010， 65 （Suppl Ⅲ）：1-27.
36.	Ramnath N， Dilling TJ， Harris LJ， et al. Treatment of stage Ⅲ non-small cell lung cancer：Diagnosis and management of lung cancer， 3rd ed. American college of chest physicians evidence-based clinical practice guidelines. Chest， 2013， 143 （5 Suppl）：314S-340S.

1. 　Martini N， Flehinger BJ， Zaman MB， et al. Prospective study of 445 lung carcinomas with mediastinal lymph node metastases. J Thorac Cardiovasc Surg， 1980 ， 80 （3）：390-399.
2. 　Cybulsky IJ， Lanza LA， Ryan MB， et al. Prognostic significance of computed tomography in resected N2 lung cancer. Ann Thorac Surg， 1992 ， 54 （3）：533-537.
3. 　Pearson FG， DeLarue NC， Ilves R， et al. Significance of positive superior mediastinal nodes identified at mediastinoscopy in patients with resectable cancer of the lung. J Thorac Cardiovasc Surg， 1982， 83 （1）：1-11.
4. 　Perez CA， Pajak TF， Rubin P， et al. Long-term observations of the patterns of failure in patients with unresectable non-oat cell carcinomaof the lung treated with definitive radiotherapy. Report by the RadiationTherapy Oncology Group. Cancer， 1987， 59 （11）：1874-1881.
5. 　Vansteenkiste J， De Leyn P， Deneffe G， et al. Present status of induction treatment in stage ⅢA-N2 non-small cell lung cancer：a review.Eur J Cardiothorac Surg， 1998， 13 （1）：1-12.
6. 　Pass HI， Pogrebniak HW， Steinberg SM， et al. Randomized trial of neoadjuvant therapy for lung cancer：interim analysis. Ann Thorac Surg， 1992， 53 （6）：992-998.
7. 　Rosell R， Gómez-Codina J， Camps C， et al. A randomized trial comparing preoperative chemotherapy plus surgery with surgery alone in patients with non-small-cell lung cancer. N Engl J Med， 1994， 330 （3）：153-158.
8. 　Roth JA， Fossella F， Komaki R， et al. A randomized trial comparingperioperative chemotherapy and surgery with surgery alone in resectablestage ⅢA non-small-cell lung cancer. J Natl Cancer Inst， 1994， 86 （9）：673-680.
9. 　Roth JA， Atkinson EN， Fossella F， et al. Long-term follow-up of patients enrolled in a randomized trial comparing perioperative chemotherapy and surgery with surgery alone in resectable stage ⅢA non-small-cell lung cancer. Lung Cancer， 1998， 21 （1）：1-6.
10. 　Depierre A， Milleron B， Moro D， et al. Phase Ⅲ trial of neo-adjuvantchemotherapy in resectable stage Ⅰ （except T1N0）， II and Ⅲa non-smallcell lung cancer：The French experience. J Clin Oncol， 2002 ， 20 （1）：247-253.
11. 　Nagai K， Tsuchiya R， Mori T， et al. A randomized trial comparing induction chemotherapy followed by surgery with surgery alone for patients with stage ⅢA N2 non-small cell lung cancer （JCOG 9209） . J Thorac Cardiovasc Surg， 2003， 125 （2）：254-260.
12. 　Pisters KM， Vallières E， Crowley JJ， et al. Surgery with or without preoperative paclitaxel and carboplatin in early-stage non-small-cell lung cancer：Southwest Oncology Group Trial S9900， an intergroup， randomized， phase Ⅲ trial. J Clin Oncol， 2010， 28 （11）：1843-1849.
13. 　Scagliotti GV， Pastorino U， Vansteenkiste JF， et al. Randomized phase Ⅲ study of surgery alone or surgery plus preoperative cisplatin and gemcitabine in stages ⅠB to ⅢA non-small-cell lung cancer. J ClinOncol， 2012 ， 30 （2）：172-178.
14. 　Dillman RO， Herndon J， Seagren SL， et al. Improved survival in stage Ⅲ non-small-cell lung cancer：seven-year follow-up of cancer and leukemia group B （CALGB） 8433 trial. J Natl Cancer Inst， 1996， 88 （17）：1210-1215.
15. 　Le Chevalier T， Arriagada R， Quoix E， et al. Radiotherapy alone versus combined chemotherapy and radiotherapy in nonresectable non-small-cell lung cancer：first analysis of a randomized trial in 353 patients. J Natl Cancer Inst， 1991， 83 （6）：417-423.
16. 　Sause W， Kolesar P， Taylor SIV， et al. Final results of phase Ⅲtrial in regionally advanced unresectable non-small cell lung cancer：Radiation therapy oncology group， eastern cooperative oncology group，and southwest oncology group. Chest， 2000， 117 （2）：358-364.
17. 　Johnstone DW， Byhardt RW， Ettinger D， et al. Phase Ⅲ study comp-aring chemotherapy and radiotherapy with preoperative chemotherapy and surgical resection in patients with non-small-cell lung Cancer with spread to mediastinal lymph nodes （N2）；final report of RTOG 89-01. Radiation therapy oncology group. Int J Radiat Oncol Biol Phys， 2002， 54 （2）：365-369.
18. 　Taylor NA， Liao ZX， Cox JD， et al. Equivalent outcome of patients with clinical stage ⅢA non-small-cell lung cancer treated with concurrent chemoradiation compared with induction chemotherapy followed by surgical resection. Int J Radiat Oncol Biol Phys， 2004， 58 （1）：204-212.
19. 　Van Meerbeeck JP， Van Schil PE， Senan S. Reply：randomized controlled trial of resection versus radiotherapy after induction chemotherapy in stage ⅢA-N2 non-small cell lung cancer. J Natl Cancer Inst，2007， 2 （12）：1138-1139.
20. 　Albain KS， Swann RS， Rusch VW， et al. Radiotherapy plus chemotherapy with or without surgical resection for stage Ⅲ non-small-cell lung cancer：a phase Ⅲ randomised controlled trial. Lancet， 2009， 374 （9687）：379-386.
21. 　Bosch-Barrera J， García-Franco C， Guillén-Grima F， et al. The multimodal management of locally advanced N2 non-small cell lung cancer：is there a role for surgical resection ? A single institution's experience. Clin Transl Oncol， 2012， 14 （11）：835-841.
22. 　Ratto GB， Costa R， Maineri P， et al. Is there a subset of patients with preoperatively diagnosed N2 non-small cell lung cancer who might benefit from surgical resection ? J Thorac Cardiovasc Surg， 2009 ， 138 （4）：849-858.
23. 　Funakoshi Y， Takeuchi Y， Kusumoto H， et al. Which subgroup of patients with pathologic N2 non-small cell lung cancer benefit from surgery ? J Cancer Res Clin Oncol， 2012， 138 （6）：1027-1033.
24. 　Sakao Y， Okumura S， Mun M， et al. Prognostic heterogeneity in multilevel N2 non-small cell lung cancer patients：importance of lymphadenopathy and occult intrapulmonary metastases. Ann Thorac Surg， 2010， 89 （4）：1060-1063.
25. 　Lorent N， De Leyn P， Lievens Y， et al. Long-term survival of surgically staged ⅢA-N2 non-small-cell lung cancer treated with surgical combined modality approach：analysis of a 7-year prospective experience. Ann Oncol， 2004， 15 （11）：1645-1653.
26. 　Stefani A， Alifano M， Bobbio A， et al. Which patients should be operated on after induction chemotherapy for N2 non-small cell lung cancer ? Analysis of a 7-year experience in 175 patients. J Thorac Cardiovasc Surg， 2010， 140 （2）：356-363.
27. 　Lococo F， Cesario A， Margaritora S， et al. Long-term results in patients with pathological complete response after induction radiochemotherapy followed by surgery for locally advanced non-small-celllung cancer. Eur J Cardiothorac Surg， 2013， 43 （3）：e71-e81.
28. 　Bueno R， Richards WG， Swanson SJ， et al. Nodal stage after induc-tion therapy for stage ⅢA lung cancer determines patient survival. AnnThorac Surg， 2000， 70 （6）：1826-1831.
29. 　Decaluwé H， De Leyn P， Vansteenkiste J， et al. Surgical multimodality treatment for baseline resectable stage ⅢA-N2 non-small cell lungcancer. Degree of mediastinal lymph node involvement and impact on survival. Eur J Cardiothorac Surg， 2009 ， 36 （3）：433-439.
30. 　Sawabata N， Keller SM， Matsumura A， et al. The impact of residualmulti-level N2 disease after induction therapy for non-small cell lung cancer. Lung Cancer， 2003， 42 （1）：69-77.
31. 　Steger V， Walker T， Mustafi M， et al. Surgery on unfavourable persistent N2/N3 non-small-cell lung cancer after trimodal therapy：do the results justify the risk ? Interact Cardiovasc Thorac Surg， 2012 ， 15 （6）：948-953.
32. 　Katakami N， Tada H， Mitsudomi T， et al. A phase 3 study of induction treatment with concurrent chemoradiotherapy versus chemotherapybefore surgery in patients with pathologically confirmed N2 stage ⅢA nonsmall cell lung cancer （WJTOG9903） . Cancer， 2012， 118 （24）：6126-6135.
33. 　Koshy M， Fedewa SA， Malik R， et al. Improved survival associated with neoadjuvant chemoradiation in patients with clinical stage ⅢA （N2）non-small-cell lung cancer. J Thorac Oncol， 2013， 8 （7）：915-922.
34. 　National Institute for Health and Clinical Excellence （NICE）. The Diagnosis and Treatment of Lung Cancer （Update）：Full Guideline. London：National Collaborating Centre for Cancer， 2011. 59-63.
35. 　Lim E， Baldwin D， Beckles M， et al. Guidelines on the radical management of patients with lung cancer：British Thoracic Society and the Society for Cardiothoracic surgery in Great Britain and Ireland.Thorax ， 2010， 65 （Suppl Ⅲ）：1-27.
36. 　Ramnath N， Dilling TJ， Harris LJ， et al. Treatment of stage Ⅲ non-small cell lung cancer：Diagnosis and management of lung cancer， 3rd ed. American college of chest physicians evidence-based clinical practice guidelines. Chest， 2013， 143 （5 Suppl）：314S-340S.

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外科治療ⅢA （N2）期非小細胞肺癌的爭議與共識

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《中國胸心血管外科臨床雜志》

外科治療ⅢA （N2）期非小細胞肺癌的爭議與共識

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