Evaluation of neoadjuvant chemotherapy for stage Ⅲa non-small cell lung cancer: A systematic review and meta-analysis_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

WANG Zhipeng , SUN Qingchao , ZHANG Haiping , ZONG Liang , REN Luying , ZHANG Yi , ZHANG Changming

The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830000, P.R.China;

Corresponding?author：

ZHANG Changming, Email:

Keywords：

Neoadjuvant; stage IIIa; non-small cell lung cancer; meta-analysis

DOI：

10.7507/1007-4848.201712003

Video：

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Objective To systematically evaluate the profitability and efficacy of neoadjuvant chemotherapy in patients with stage Ⅲa non-small cell lung cancer. Methods Randomized controlled trials (RCT) on neoadjuvant chemotherapy for stage Ⅲa non-small cell lung cancer were collected from WangFang Data database, Web of Science, PubMed, EMbase, CNKI, The Cochrane Library, VIP and CBM databases. From building to October 2017. After two independent reviewers screened the literature, extracted data and assessed the risk of being included in the study, Meta-analysis was performed using RevMan 5.3 software. Results A total of 15 RCT were included, including 1899 non-small cell lung cancer patients. The results of Meta analysis showed that the resection rate of R0 in neoadjuvant chemotherapy group was significantly higher than that in control group (OR=2.04, 95%CI 1.52 to 2.74, P<0.05), and there was no significant difference in postoperative complications between two groups (OR=1.23, 95%CI 0.89 to 1.69, P=0.22). In terms of survival rate, the neoadjuvant chemotherapy group could improve patients for one year (OR=1.38, 95%CI 1.01 to 1.88, P=0.04), three years (OR=1.57, 95%CI 1.16 to 2.12, P=0.004) and 5 years survival rate (OR=2.09, 95%CI 1.24 to 3.53, P=0.005) significance of learning. Conclusion Compared with the control group, neoadjuvant chemotherapy can improve the surgical R0 resection rate and the one, three and five year survival rate of patients with stage Ⅲa non-small cell lung cancer without increasing the postoperative complications. Due to the quantity and quality limitations of the included studies, the above conclusion still needs to be verified by more high-quality research.

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2.	Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin, 2016, 66(2): 115-132.
3.	Piperis M, Tsoukalas N. Stereotactic body radiation therapy and surgery for early stage non-small cell lung cancer. J Invest Surg, 2017: 1-3.
4.	Berkovic P, Paelinck L, Gulyban A, et al. Adaptive radiotherapy for locally advanced non-small cell lung cancer: dosimetric gain and treatment outcome prediction. Acta Oncol, 2017, 56(11): 1656-1659.
5.	Pless M, Stupp R, Ris HB, et al. Induction chemoradiation in stage IIIA/N2 non-small-cell lung cancer: a phase 3 randomised trial. Lancet, 2015, 386(9998): 1049-1056.
6.	Zhao X, Wen X, Wei W, et al. Predictors for the efficacy of Endostar combined with neoadjuvant chemotherapy for stage IIIA (N2) NSCLC. Cancer Biomark, 2017, 21(1): 169-177.
7.	Savic M, Kontic M, Ercegovac M, et al. Comparison of mediastinal lymph node status and relapse pattern in clinical stage IIIA non-small cell lung cancer patients treated with neoadjuvant chemotherapy versus upfront surgery: A single center experience. Thorac Cancer, 2017, 8(5): 393-401.
8.	Wang HH, Deng L, Wen QL, et al. Early postoperative radiotherapy is associated with improved outcomes over late postoperative radiotherapy in the management of completely resected (R0) Stage IIIA-N2 non-small cell lung cancer. Oncotarget, 2017, 8(38): 62998-63013.
9.	Higgins JP, Green S. Cochrane Handbook for Systematic Reviews of Interventions (Version 5.1.0). Available at:http://handbook.cochrane.org.
10.	唐翠萍, 秦思, 伍萬春, 等. Ⅲa 期非小細胞肺癌新輔助化療的療效分析及應用價值.中國肺癌雜志, 2017, 20(2): 100-106.
11.	陳樹興, 陳新富, 郭立人, 等.ⅢA 期非小細胞肺癌患者術前新輔助化療的臨床分析.福建醫藥雜志, 2013, 35(6): 118-120.
12.	溫永富, 宋旭東. Ⅲa 期非小細胞肺癌新輔助化療的臨床評價.中國綜合臨床, 2005, 21(7): 624-625.
13.	石鵬飛, 張曉明. MVP 方案新輔助化療治療ⅢA 期非小細胞肺癌的療效觀察.實用癌癥雜志, 2016, 31(5): 769-771.
14.	張國慶, 韓峰, 高勝利, 等.新輔助化療對 165 例 Ⅲa 期非小細胞肺癌患者術后生存的影響分析. 腫瘤研究與臨床, 2007, 19(7): 470-473.
15.	周明, 王遠東, 邵中夫, 等. 新輔助化療對 Ⅲa 期非小細胞肺癌手術及圍術期并發癥的影響.廣東醫學, 2004, 25(9): 1053-1054.
16.	李勇生, 楊文東, 黃宇康, 等.新輔助化療對ⅢA 期非小細胞肺癌手術療效的影響. 中國基層醫藥, 2006, 13(2): 201-202.
17.	李堅, 俞力超, 張德厚, 等.新輔助化療對提高ⅢA 期非小細胞肺癌手術切除率的作用.中國腫瘤臨床與康復, 2002, 9(6): 67-69.
18.	游慶軍, 王嘉瑋, 蔣錫初, 等.新輔助化療在 Ⅲa 期非小細胞肺癌治療中的應用.現代腫瘤醫學, 2006, 14(7): 827-828.
19.	王嘉瑋, 游慶軍, 蔣錫初, 等.新輔助化療在 Ⅲa 期肺癌治療中的應用. 實用全科醫學, 2006, 4(1): 15-16.
20.	張艷峰, 蘇文中.新輔助化療治療 Ⅲa 期非小細胞肺癌的臨床觀察. 中國繼續醫學教育, 2015, (3): 66-67.
21.	李宇暉, 高爽, 莊思敏, 等.紫杉醇加順鉑的新輔助化療對提高ⅢA 期非小細胞肺癌手術切除率的臨床作用. 嶺南現代臨床外科, 2004, 4(3): 231-232.
22.	張立新, 王啟文, 曲明江, 等.新輔助化療對 IIIA 期非小細胞肺癌外科治療的影響. 中國誤診學雜志, 2011, 11(30): 7401-7402.
23.	Milroy R, Macbeth F. Neoadjuvant chemotherapy in stage IIIa non-small cell lung cancer. Thorax, 1995, 50 Suppl 1: S25-S30.
24.	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.
25.	Misumi K, Harada H, Tsubokawa N, et al. Clinical benefit of neoadjuvant chemoradiotherapy for the avoidance of pneumonectomy; assessment in 12 consecutive centrally located non-small cell lung cancers. Gen Thorac Cardiovasc Surg, 2017, 65(7): 392-399.
26.	Tang C, Qin S, Wu W, et al. Efficacy and Potential Application of Neoadjuvant Chemotherapy in Patients with IIIa Stage Non-small Cell Lung Cancer. Zhongguo Fei Ai Za Zhi, 2017, 20(2): 100-106.
27.	Wang Y, Wang X, Yan S, et al. Progress of neoadjuvant therapy combined with surgery in non-small cell lung cancer. Zhongguo Fei Ai Za Zhi, 2017, 20(5): 352-360.
28.	Bruzzi JF, Komaki R, Walsh GL, et al. Imaging of non-small cell lung cancer of the superior sulcus: part 1: anatomy, clinical manifestations, and management. Radiographics, 2008, 28(2): 551-560.
29.	Duan X, Liu Z, Xu S. Research progresses of circulating tumor cells in diagnosis and treatment of early lung cancer. zhongguo fei ai za zhi, 2017, 20(10): 703-709.
30.	Spaggiari L, Casiraghi M, Guarize J, et al. Outcome of Patients With pN2 " Potentially Resectable” Nonsmall Cell Lung Cancer Who Underwent Surgery After Induction Chemotherapy. Semin Thorac Cardiovasc Surg, 2016, 28(2): 593-602.
31.	Francolini G, Ferrari K, Scotti V. Neoadjuvant approach for nonsmall cell lung cancer: overview of the current issues. Curr Opin Oncol, 2017, 29(2): 123-128.
32.	Zhu J, Zhang HP, Jiang S, et al. Neoadjuvant chemotherapy by bronchial arterial infusion in patients with unresectable stage III squamous cell lung cancer. Ther Adv Respir Dis, 2017, 11(8): 301-309.

1. Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012. CA Cancer J Clin, 2015, 65(2): 87-108.
2. Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin, 2016, 66(2): 115-132.
3. Piperis M, Tsoukalas N. Stereotactic body radiation therapy and surgery for early stage non-small cell lung cancer. J Invest Surg, 2017: 1-3.
4. Berkovic P, Paelinck L, Gulyban A, et al. Adaptive radiotherapy for locally advanced non-small cell lung cancer: dosimetric gain and treatment outcome prediction. Acta Oncol, 2017, 56(11): 1656-1659.
5. Pless M, Stupp R, Ris HB, et al. Induction chemoradiation in stage IIIA/N2 non-small-cell lung cancer: a phase 3 randomised trial. Lancet, 2015, 386(9998): 1049-1056.
6. Zhao X, Wen X, Wei W, et al. Predictors for the efficacy of Endostar combined with neoadjuvant chemotherapy for stage IIIA (N2) NSCLC. Cancer Biomark, 2017, 21(1): 169-177.
7. Savic M, Kontic M, Ercegovac M, et al. Comparison of mediastinal lymph node status and relapse pattern in clinical stage IIIA non-small cell lung cancer patients treated with neoadjuvant chemotherapy versus upfront surgery: A single center experience. Thorac Cancer, 2017, 8(5): 393-401.
8. Wang HH, Deng L, Wen QL, et al. Early postoperative radiotherapy is associated with improved outcomes over late postoperative radiotherapy in the management of completely resected (R0) Stage IIIA-N2 non-small cell lung cancer. Oncotarget, 2017, 8(38): 62998-63013.
9. Higgins JP, Green S. Cochrane Handbook for Systematic Reviews of Interventions (Version 5.1.0). Available at:http://handbook.cochrane.org.
10. 唐翠萍, 秦思, 伍萬春, 等. Ⅲa 期非小細胞肺癌新輔助化療的療效分析及應用價值.中國肺癌雜志, 2017, 20(2): 100-106.
11. 陳樹興, 陳新富, 郭立人, 等.ⅢA 期非小細胞肺癌患者術前新輔助化療的臨床分析.福建醫藥雜志, 2013, 35(6): 118-120.
12. 溫永富, 宋旭東. Ⅲa 期非小細胞肺癌新輔助化療的臨床評價.中國綜合臨床, 2005, 21(7): 624-625.
13. 石鵬飛, 張曉明. MVP 方案新輔助化療治療ⅢA 期非小細胞肺癌的療效觀察.實用癌癥雜志, 2016, 31(5): 769-771.
14. 張國慶, 韓峰, 高勝利, 等.新輔助化療對 165 例 Ⅲa 期非小細胞肺癌患者術后生存的影響分析. 腫瘤研究與臨床, 2007, 19(7): 470-473.
15. 周明, 王遠東, 邵中夫, 等. 新輔助化療對 Ⅲa 期非小細胞肺癌手術及圍術期并發癥的影響.廣東醫學, 2004, 25(9): 1053-1054.
16. 李勇生, 楊文東, 黃宇康, 等.新輔助化療對ⅢA 期非小細胞肺癌手術療效的影響. 中國基層醫藥, 2006, 13(2): 201-202.
17. 李堅, 俞力超, 張德厚, 等.新輔助化療對提高ⅢA 期非小細胞肺癌手術切除率的作用.中國腫瘤臨床與康復, 2002, 9(6): 67-69.
18. 游慶軍, 王嘉瑋, 蔣錫初, 等.新輔助化療在 Ⅲa 期非小細胞肺癌治療中的應用.現代腫瘤醫學, 2006, 14(7): 827-828.
19. 王嘉瑋, 游慶軍, 蔣錫初, 等.新輔助化療在 Ⅲa 期肺癌治療中的應用. 實用全科醫學, 2006, 4(1): 15-16.
20. 張艷峰, 蘇文中.新輔助化療治療 Ⅲa 期非小細胞肺癌的臨床觀察. 中國繼續醫學教育, 2015, (3): 66-67.
21. 李宇暉, 高爽, 莊思敏, 等.紫杉醇加順鉑的新輔助化療對提高ⅢA 期非小細胞肺癌手術切除率的臨床作用. 嶺南現代臨床外科, 2004, 4(3): 231-232.
22. 張立新, 王啟文, 曲明江, 等.新輔助化療對 IIIA 期非小細胞肺癌外科治療的影響. 中國誤診學雜志, 2011, 11(30): 7401-7402.
23. Milroy R, Macbeth F. Neoadjuvant chemotherapy in stage IIIa non-small cell lung cancer. Thorax, 1995, 50 Suppl 1: S25-S30.
24. 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.
25. Misumi K, Harada H, Tsubokawa N, et al. Clinical benefit of neoadjuvant chemoradiotherapy for the avoidance of pneumonectomy; assessment in 12 consecutive centrally located non-small cell lung cancers. Gen Thorac Cardiovasc Surg, 2017, 65(7): 392-399.
26. Tang C, Qin S, Wu W, et al. Efficacy and Potential Application of Neoadjuvant Chemotherapy in Patients with IIIa Stage Non-small Cell Lung Cancer. Zhongguo Fei Ai Za Zhi, 2017, 20(2): 100-106.
27. Wang Y, Wang X, Yan S, et al. Progress of neoadjuvant therapy combined with surgery in non-small cell lung cancer. Zhongguo Fei Ai Za Zhi, 2017, 20(5): 352-360.
28. Bruzzi JF, Komaki R, Walsh GL, et al. Imaging of non-small cell lung cancer of the superior sulcus: part 1: anatomy, clinical manifestations, and management. Radiographics, 2008, 28(2): 551-560.
29. Duan X, Liu Z, Xu S. Research progresses of circulating tumor cells in diagnosis and treatment of early lung cancer. zhongguo fei ai za zhi, 2017, 20(10): 703-709.
30. Spaggiari L, Casiraghi M, Guarize J, et al. Outcome of Patients With pN2 " Potentially Resectable” Nonsmall Cell Lung Cancer Who Underwent Surgery After Induction Chemotherapy. Semin Thorac Cardiovasc Surg, 2016, 28(2): 593-602.
31. Francolini G, Ferrari K, Scotti V. Neoadjuvant approach for nonsmall cell lung cancer: overview of the current issues. Curr Opin Oncol, 2017, 29(2): 123-128.
32. Zhu J, Zhang HP, Jiang S, et al. Neoadjuvant chemotherapy by bronchial arterial infusion in patients with unresectable stage III squamous cell lung cancer. Ther Adv Respir Dis, 2017, 11(8): 301-309.

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