The efficacy and safety of concurrent versus sequential chemoradiotherapy for locally advanced non-small cell lung cancer: A systematic review and meta-analysis_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

YANG Kai ^1,2 , DOU Li ² , CAO Wei ^1,2 , JIN Dacheng ² , WANG Qi ^1,2 ,  GOU Yunjiu ²

1. First Clinical Medical School, Gansu University of Chinese Medicine, Lanzhou, 730000, P. R. China;
2. First Department of Thoracic Surgery, Gansu Provincial Hospital, Lanzhou, 730000, P. R. China;

Corresponding?author：

GOU Yunjiu, Email: gouyunjiu@163.com

Keywords：

Non-small cell lung cancer; synchronous; sequential; chemoradiotherapy; systematic review/meta-analysis

DOI：

10.7507/1007-4848.202312016

Video：

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Objective To evaluate the efficacy and safety of concurrent chemoradiotherapy versus sequential chemoradiotherapy in the treatment of locally advanced non-small cell lung cancer. Methods The relevant literature was searched in PubMed, Web of Science, CNKI and Wanfang databases from the inception to October 15, 2023, and the literature was screened according to the inclusion and exclusion criteria. Review Manager 5.3 software was used for meta-analysis of the literature, and the Cochrane bias risk assessment tool was used to evaluate the quality of the literature. Results Finally, 14 randomized controlled studies were included covering a total of 1048 patients. The results of meta-analysis showed that the overall response rate [OR=2.39, 95%CI (1.83, 3.11)], 1-year survival rate [OR=1.81, 95%CI (1.39, 2.35)], 2-year survival rate [OR=1.75, 95%CI (1.27, 2.42)] and 3-year survival rate [OR=2.33, 95%CI (1.49, 3.66)] were superior to sequential chemoradiotherapy, and the difference was statistically significant (P<0.05). In terms of safety, concurrent chemoradiotherapy increased the incidence of radiation esophagitis (P<0.05), but there was no statistical difference in the incidence of leukopenia and radiation pneumonia (P>0.05). Conclusion For patients with locally advanced non-small cell lung cancer, the short-term efficacy of concurrent chemoradiotherapy is better than that of sequential chemoradiotherapy and can improve the 1-, 2- and 3-year survival rates, but the toxic side effects of the treatment are slightly greater than those of the sequential chemoradiotherapy.

1.	Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021, 71(3): 209-249.
2.	Chen P, Liu Y, Wen Y, et al. Non-small cell lung cancer in China. Cancer Commun (Lond), 2022, 42(10): 937-970.
3.	Gridelli C, Rossi A, Carbone DP, et al. Non-small-cell lung cancer. Nat Rev Dis Primers. 2015, 1: 15009.
4.	Guo Q, Liu L, Chen Z, et al. Current treatments for non-small cell lung cancer. Front Oncol, 2022, 12: 945102.
5.	Kim HC, Ji W, Lee JC, et al. Prognostic factor and clinical outcome in stage Ⅲ non-small cell lung cancer: A study based on real-world clinical data in the Korean population. Cancer Res Treat, 2021, 53(4): 1033-1041.
6.	Vansteenkiste J, De Ruysscher D, Eberhardt WE, et al. Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol, 2013, Suppl 6: vi89-vi98.
7.	Atagi S, Kawahara M, Yokoyama A, et al. Thoracic radiotherapy with or without daily low-dose carboplatin in elderly patients with non-small-cell lung cancer: A randomised, controlled, phase 3 trial by the Japan Clinical Oncology Group (JCOG0301). Lancet Oncol, 2012, 13(7): 671-678.
8.	Dawe DE, Christiansen D, Swaminath A, et al. Chemoradiotherapy versus radiotherapy alone in elderly patients with stageⅢnon-small cell lung cancer: A systematic review and meta-analysis. Lung Cancer, 2016, 99: 180-185.
9.	O'Rourke N, Roqué I Figuls M, Farré Bernadó N, et al. Concurrent chemoradiotherapy in non-small cell lung cancer. Cochrane Database Syst Rev, 2010, 6: CD002140.
10.	Verfaillie S, Lambrecht M, Berkovic P, et al. Treatment of unresectable stageⅢNSCLC: Real world cohort study and literature review. Cancer Treat Res Commun, 2023, 36: 100727.
11.	Furuse K, Fukuoka M, Kawahara M, et al. PhaseⅢstudy of concurrent versus sequential thoracic radiotherapy in combination with mitomycin, vindesine, and cisplatin in unresectable stageⅢnon-small-cell lung cancer. J Clin Oncol, 1999, 17(9): 2692-2699.
12.	Hung MS, Wu YF, Chen YC. Efficacy of chemoradiotherapy versus radiation alone in patients with inoperable locally advanced non-small-cell lung cancer: A meta-analysis and systematic review. Medicine (Baltimore), 2019, 98(27): e16167.
13.	Bruni A, Giaj-Levra N, Ciammella P, et al. Management of locally advanced non-small cell lung cancer in the modern era: A national Italian survey on diagnosis, treatment and multidisciplinary approach. PLoS One, 2019, 14(11): e0224027.
14.	Gadgeel SM, Ruckdeschel JC, Patel BB, et al. PhaseⅡstudy of pemetrexed and cisplatin, with chest radiotherapy followed by docetaxel in patients with stageⅢnon-small cell lung cancer. J Thorac Oncol, 2011, 6(5): 927-933.
15.	朱禮, 吳榮. Ⅲ期非小細胞肺癌同期放化療與序貫放化療的對照研究. 中華腫瘤防治雜志, 2009, 16(14): 1105-1107.
16.	張西, 李浩, 周從明, 等. 吉西他濱和順鉑方案同步三維適形放療治療局部晚期非小細胞肺癌的臨床研究. 中國臨床藥理學雜志, 2014, 30(4): 300-302.
17.	楊杰, 季海峰, 王勇. 長春瑞濱聯合同步三維適形放療治療局部晚期非小細胞肺癌的臨床研究. 中國臨床實用醫學, 2009, 3(7): 63-64.
18.	陽美玲. 紫杉醇配伍順鉑化療聯合放療同步與序貫治療晚期非小細胞肺癌的對比研究. 世界臨床醫學, 2017, 11(20): 85, 89.
19.	王忠民. 晚期非小細胞肺癌三維適形放療與紫杉醇加順鉑同期化療和序貫化療的對比觀察. 現代醫藥衛生, 2011, 27(6): 844-845.
20.	王玉洲, 楊志雄, 廖思海, 等. 同步放化療治療局部晚期非小細胞肺癌的Ⅲ期臨床研究. 臨床腫瘤學雜志, 2009, 14(5): 390-395.
21.	王頌平, 宋海平, 徐建華, 等. 多西他賽聯合順鉑同步放療治療局部晚期非小細胞肺癌隨機對照臨床研究. 中國腫瘤臨床, 2009, 36(13): 736-739.
22.	王鵬遠. 序貫化放療與同步化放療治療Ⅲ期非小細胞肺癌療效觀察. 醫學信息(上旬刊), 2011, 24(9): 5704-5706.
23.	李紅波, 盧緒菁, 湯華, 等. 放化療同步與序貫治療局部晚期非小細胞肺癌臨床療效比較. 臨床醫學工程, 2011, 18(6): 878-879.
24.	賈正飛, 馮永, 仲琴, 等. 多西紫杉醇/順鉑化療同步放療對局部晚期非小細胞肺癌療效觀察. 山東大學學報(醫學版), 2008, 46(9): 898-900.
25.	侯良寶, 王守林, 王清, 等. 超分割放療同步化療治療Ⅲ期非小細胞肺癌. 中國腫瘤臨床與康復, 2006, 13(4): 322-324.
26.	高亞麗. 同步和序貫放化療治療Ⅲ期非小細胞肺癌的比較分析. 腫瘤基礎與臨床, 2011, 24(1): 29-31.
27.	房麗, 王紅陽, 王玲玲, 等. 放化療聯合治療局部晚期非小細胞肺癌臨床療效觀察. 臨床肺科雜志, 2014(7): 1291-1294.
28.	白樺, 侯敏全, 白曉寧. 同步放化療與序貫化放療治療Ⅲ期不能手術非小細胞肺癌的臨床療效. 昆明醫科大學學報, 2015, 36(6): 42-45.
29.	石安輝, 朱廣迎. 局部晚期非小細胞肺癌放化療的現狀與進展. 臨床外科雜志, 2016, 24(7): 505-508.
30.	Aupérin A, Le Péchoux C, Rolland E, et al. Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer. J Clin Oncol, 2010, 28(13): 2181-2190.
31.	Curran WJ, Paulus R, Langer CJ, et al. Sequential vs. concurrent chemoradiation for stageⅢnon-small cell lung cancer: Randomized phaseⅢtrial RTOG 9410. J Natl Cancer Inst, 2011, 103(19): 1452-1460.
32.	Belderbos J, Uitterhoeve L, van Zandwijk N, et al. Randomised trial of sequential versus concurrent chemo-radiotherapy in patients with inoperable non-small cell lung cancer (EORTC 08972-22973). Eur J Cancer, 2007, 43(1): 114-121.
33.	Chang SC, Lai YC, Hung JC, et al. Oral glutamine supplements reduce concurrent chemoradiotherapy-induced esophagitis in patients with advanced non-small cell lung cancer. Medicine (Baltimore), 2019, 98(8): e14463.
34.	任維維, 米登海, 李征, 等. 非小細胞肺癌紫杉醇類聯合順鉑同步或序貫放化療對比的Meta分析. 中華腫瘤防治雜志, 2013, 20(5): 377-382.
35.	Zheng Q, Min S, Zhou Y. A network meta-analysis for efficacies and toxicities of different concurrent chemoradiotherapy regimens in the treatment of locally advanced non-small cell lung cancer. BMC Cancer, 2022, 22(1): 674.
36.	Palma DA, Senan S, Tsujino K, et al. Predicting radiation pneumonitis after chemoradiation therapy for lung cancer: An international individual patient data meta-analysis. Int J Radiat Oncol Biol Phys, 2013, 85(2): 444-450.
37.	Parashar B, Edwards A, Mehta R, et al. Chemotherapy significantly increases the risk of radiation pneumonitis in radiation therapy of advanced lung cancer. Am J Clin Oncol, 2011, 34(2): 160-164.
38.	岳清. 局限期小細胞肺癌同步放化療與序貫放化療的Meta分析. 吉林大學, 2014.
39.	王毓洲, 應紅艷, 趙林, 等. 局部晚期非小細胞肺癌同步化放療與序貫化放療比較的Meta分析. 循證醫學, 2007, 7(3): 152-157.

1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021, 71(3): 209-249.
2. Chen P, Liu Y, Wen Y, et al. Non-small cell lung cancer in China. Cancer Commun (Lond), 2022, 42(10): 937-970.
3. Gridelli C, Rossi A, Carbone DP, et al. Non-small-cell lung cancer. Nat Rev Dis Primers. 2015, 1: 15009.
4. Guo Q, Liu L, Chen Z, et al. Current treatments for non-small cell lung cancer. Front Oncol, 2022, 12: 945102.
5. Kim HC, Ji W, Lee JC, et al. Prognostic factor and clinical outcome in stage Ⅲ non-small cell lung cancer: A study based on real-world clinical data in the Korean population. Cancer Res Treat, 2021, 53(4): 1033-1041.
6. Vansteenkiste J, De Ruysscher D, Eberhardt WE, et al. Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol, 2013, Suppl 6: vi89-vi98.
7. Atagi S, Kawahara M, Yokoyama A, et al. Thoracic radiotherapy with or without daily low-dose carboplatin in elderly patients with non-small-cell lung cancer: A randomised, controlled, phase 3 trial by the Japan Clinical Oncology Group (JCOG0301). Lancet Oncol, 2012, 13(7): 671-678.
8. Dawe DE, Christiansen D, Swaminath A, et al. Chemoradiotherapy versus radiotherapy alone in elderly patients with stageⅢnon-small cell lung cancer: A systematic review and meta-analysis. Lung Cancer, 2016, 99: 180-185.
9. O'Rourke N, Roqué I Figuls M, Farré Bernadó N, et al. Concurrent chemoradiotherapy in non-small cell lung cancer. Cochrane Database Syst Rev, 2010, 6: CD002140.
10. Verfaillie S, Lambrecht M, Berkovic P, et al. Treatment of unresectable stageⅢNSCLC: Real world cohort study and literature review. Cancer Treat Res Commun, 2023, 36: 100727.
11. Furuse K, Fukuoka M, Kawahara M, et al. PhaseⅢstudy of concurrent versus sequential thoracic radiotherapy in combination with mitomycin, vindesine, and cisplatin in unresectable stageⅢnon-small-cell lung cancer. J Clin Oncol, 1999, 17(9): 2692-2699.
12. Hung MS, Wu YF, Chen YC. Efficacy of chemoradiotherapy versus radiation alone in patients with inoperable locally advanced non-small-cell lung cancer: A meta-analysis and systematic review. Medicine (Baltimore), 2019, 98(27): e16167.
13. Bruni A, Giaj-Levra N, Ciammella P, et al. Management of locally advanced non-small cell lung cancer in the modern era: A national Italian survey on diagnosis, treatment and multidisciplinary approach. PLoS One, 2019, 14(11): e0224027.
14. Gadgeel SM, Ruckdeschel JC, Patel BB, et al. PhaseⅡstudy of pemetrexed and cisplatin, with chest radiotherapy followed by docetaxel in patients with stageⅢnon-small cell lung cancer. J Thorac Oncol, 2011, 6(5): 927-933.
15. 朱禮, 吳榮. Ⅲ期非小細胞肺癌同期放化療與序貫放化療的對照研究. 中華腫瘤防治雜志, 2009, 16(14): 1105-1107.
16. 張西, 李浩, 周從明, 等. 吉西他濱和順鉑方案同步三維適形放療治療局部晚期非小細胞肺癌的臨床研究. 中國臨床藥理學雜志, 2014, 30(4): 300-302.
17. 楊杰, 季海峰, 王勇. 長春瑞濱聯合同步三維適形放療治療局部晚期非小細胞肺癌的臨床研究. 中國臨床實用醫學, 2009, 3(7): 63-64.
18. 陽美玲. 紫杉醇配伍順鉑化療聯合放療同步與序貫治療晚期非小細胞肺癌的對比研究. 世界臨床醫學, 2017, 11(20): 85, 89.
19. 王忠民. 晚期非小細胞肺癌三維適形放療與紫杉醇加順鉑同期化療和序貫化療的對比觀察. 現代醫藥衛生, 2011, 27(6): 844-845.
20. 王玉洲, 楊志雄, 廖思海, 等. 同步放化療治療局部晚期非小細胞肺癌的Ⅲ期臨床研究. 臨床腫瘤學雜志, 2009, 14(5): 390-395.
21. 王頌平, 宋海平, 徐建華, 等. 多西他賽聯合順鉑同步放療治療局部晚期非小細胞肺癌隨機對照臨床研究. 中國腫瘤臨床, 2009, 36(13): 736-739.
22. 王鵬遠. 序貫化放療與同步化放療治療Ⅲ期非小細胞肺癌療效觀察. 醫學信息(上旬刊), 2011, 24(9): 5704-5706.
23. 李紅波, 盧緒菁, 湯華, 等. 放化療同步與序貫治療局部晚期非小細胞肺癌臨床療效比較. 臨床醫學工程, 2011, 18(6): 878-879.
24. 賈正飛, 馮永, 仲琴, 等. 多西紫杉醇/順鉑化療同步放療對局部晚期非小細胞肺癌療效觀察. 山東大學學報(醫學版), 2008, 46(9): 898-900.
25. 侯良寶, 王守林, 王清, 等. 超分割放療同步化療治療Ⅲ期非小細胞肺癌. 中國腫瘤臨床與康復, 2006, 13(4): 322-324.
26. 高亞麗. 同步和序貫放化療治療Ⅲ期非小細胞肺癌的比較分析. 腫瘤基礎與臨床, 2011, 24(1): 29-31.
27. 房麗, 王紅陽, 王玲玲, 等. 放化療聯合治療局部晚期非小細胞肺癌臨床療效觀察. 臨床肺科雜志, 2014(7): 1291-1294.
28. 白樺, 侯敏全, 白曉寧. 同步放化療與序貫化放療治療Ⅲ期不能手術非小細胞肺癌的臨床療效. 昆明醫科大學學報, 2015, 36(6): 42-45.
29. 石安輝, 朱廣迎. 局部晚期非小細胞肺癌放化療的現狀與進展. 臨床外科雜志, 2016, 24(7): 505-508.
30. Aupérin A, Le Péchoux C, Rolland E, et al. Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer. J Clin Oncol, 2010, 28(13): 2181-2190.
31. Curran WJ, Paulus R, Langer CJ, et al. Sequential vs. concurrent chemoradiation for stageⅢnon-small cell lung cancer: Randomized phaseⅢtrial RTOG 9410. J Natl Cancer Inst, 2011, 103(19): 1452-1460.
32. Belderbos J, Uitterhoeve L, van Zandwijk N, et al. Randomised trial of sequential versus concurrent chemo-radiotherapy in patients with inoperable non-small cell lung cancer (EORTC 08972-22973). Eur J Cancer, 2007, 43(1): 114-121.
33. Chang SC, Lai YC, Hung JC, et al. Oral glutamine supplements reduce concurrent chemoradiotherapy-induced esophagitis in patients with advanced non-small cell lung cancer. Medicine (Baltimore), 2019, 98(8): e14463.
34. 任維維, 米登海, 李征, 等. 非小細胞肺癌紫杉醇類聯合順鉑同步或序貫放化療對比的Meta分析. 中華腫瘤防治雜志, 2013, 20(5): 377-382.
35. Zheng Q, Min S, Zhou Y. A network meta-analysis for efficacies and toxicities of different concurrent chemoradiotherapy regimens in the treatment of locally advanced non-small cell lung cancer. BMC Cancer, 2022, 22(1): 674.
36. Palma DA, Senan S, Tsujino K, et al. Predicting radiation pneumonitis after chemoradiation therapy for lung cancer: An international individual patient data meta-analysis. Int J Radiat Oncol Biol Phys, 2013, 85(2): 444-450.
37. Parashar B, Edwards A, Mehta R, et al. Chemotherapy significantly increases the risk of radiation pneumonitis in radiation therapy of advanced lung cancer. Am J Clin Oncol, 2011, 34(2): 160-164.
38. 岳清. 局限期小細胞肺癌同步放化療與序貫放化療的Meta分析. 吉林大學, 2014.
39. 王毓洲, 應紅艷, 趙林, 等. 局部晚期非小細胞肺癌同步化放療與序貫化放療比較的Meta分析. 循證醫學, 2007, 7(3): 152-157.

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