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.	朱礼, 吴荣. Ⅲ期非小细胞肺癌同期放化疗与序贯放化疗的对照研究. 中华肿瘤防治杂志, 2009, 16(14): 1105-1107.
16.	张西, 李浩, 周从明, 等. 吉西他滨和顺铂方案同步三维适形放疗治疗局部晚期非小细胞肺癌的临床研究. 中国临床药理学杂志, 2014, 30(4): 300-302.
17.	杨杰, 季海峰, 王勇. 长春瑞滨联合同步三维适形放疗治疗局部晚期非小细胞肺癌的临床研究. 中国临床实用医学, 2009, 3(7): 63-64.
18.	阳美玲. 紫杉醇配伍顺铂化疗联合放疗同步与序贯治疗晚期非小细胞肺癌的对比研究. 世界临床医学, 2017, 11(20): 85, 89.
19.	王忠民. 晚期非小细胞肺癌三维适形放疗与紫杉醇加顺铂同期化疗和序贯化疗的对比观察. 现代医药卫生, 2011, 27(6): 844-845.
20.	王玉洲, 杨志雄, 廖思海, 等. 同步放化疗治疗局部晚期非小细胞肺癌的Ⅲ期临床研究. 临床肿瘤学杂志, 2009, 14(5): 390-395.
21.	王颂平, 宋海平, 徐建华, 等. 多西他赛联合顺铂同步放疗治疗局部晚期非小细胞肺癌随机对照临床研究. 中国肿瘤临床, 2009, 36(13): 736-739.
22.	王鹏远. 序贯化放疗与同步化放疗治疗Ⅲ期非小细胞肺癌疗效观察. 医学信息(上旬刊), 2011, 24(9): 5704-5706.
23.	李红波, 卢绪菁, 汤华, 等. 放化疗同步与序贯治疗局部晚期非小细胞肺癌临床疗效比较. 临床医学工程, 2011, 18(6): 878-879.
24.	贾正飞, 冯永, 仲琴, 等. 多西紫杉醇/顺铂化疗同步放疗对局部晚期非小细胞肺癌疗效观察. 山东大学学报(医学版), 2008, 46(9): 898-900.
25.	侯良宝, 王守林, 王清, 等. 超分割放疗同步化疗治疗Ⅲ期非小细胞肺癌. 中国肿瘤临床与康复, 2006, 13(4): 322-324.
26.	高亚丽. 同步和序贯放化疗治疗Ⅲ期非小细胞肺癌的比较分析. 肿瘤基础与临床, 2011, 24(1): 29-31.
27.	房丽, 王红阳, 王玲玲, 等. 放化疗联合治疗局部晚期非小细胞肺癌临床疗效观察. 临床肺科杂志, 2014(7): 1291-1294.
28.	白桦, 侯敏全, 白晓宁. 同步放化疗与序贯化放疗治疗Ⅲ期不能手术非小细胞肺癌的临床疗效. 昆明医科大学学报, 2015, 36(6): 42-45.
29.	石安辉, 朱广迎. 局部晚期非小细胞肺癌放化疗的现状与进展. 临床外科杂志, 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.	任维维, 米登海, 李征, 等. 非小细胞肺癌紫杉醇类联合顺铂同步或序贯放化疗对比的Meta分析. 中华肿瘤防治杂志, 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. 局限期小细胞肺癌同步放化疗与序贯放化疗的Meta分析. 吉林大学, 2014.
39.	王毓洲, 应红艳, 赵林, 等. 局部晚期非小细胞肺癌同步化放疗与序贯化放疗比较的Meta分析. 循证医学, 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. 朱礼, 吴荣. Ⅲ期非小细胞肺癌同期放化疗与序贯放化疗的对照研究. 中华肿瘤防治杂志, 2009, 16(14): 1105-1107.
16. 张西, 李浩, 周从明, 等. 吉西他滨和顺铂方案同步三维适形放疗治疗局部晚期非小细胞肺癌的临床研究. 中国临床药理学杂志, 2014, 30(4): 300-302.
17. 杨杰, 季海峰, 王勇. 长春瑞滨联合同步三维适形放疗治疗局部晚期非小细胞肺癌的临床研究. 中国临床实用医学, 2009, 3(7): 63-64.
18. 阳美玲. 紫杉醇配伍顺铂化疗联合放疗同步与序贯治疗晚期非小细胞肺癌的对比研究. 世界临床医学, 2017, 11(20): 85, 89.
19. 王忠民. 晚期非小细胞肺癌三维适形放疗与紫杉醇加顺铂同期化疗和序贯化疗的对比观察. 现代医药卫生, 2011, 27(6): 844-845.
20. 王玉洲, 杨志雄, 廖思海, 等. 同步放化疗治疗局部晚期非小细胞肺癌的Ⅲ期临床研究. 临床肿瘤学杂志, 2009, 14(5): 390-395.
21. 王颂平, 宋海平, 徐建华, 等. 多西他赛联合顺铂同步放疗治疗局部晚期非小细胞肺癌随机对照临床研究. 中国肿瘤临床, 2009, 36(13): 736-739.
22. 王鹏远. 序贯化放疗与同步化放疗治疗Ⅲ期非小细胞肺癌疗效观察. 医学信息(上旬刊), 2011, 24(9): 5704-5706.
23. 李红波, 卢绪菁, 汤华, 等. 放化疗同步与序贯治疗局部晚期非小细胞肺癌临床疗效比较. 临床医学工程, 2011, 18(6): 878-879.
24. 贾正飞, 冯永, 仲琴, 等. 多西紫杉醇/顺铂化疗同步放疗对局部晚期非小细胞肺癌疗效观察. 山东大学学报(医学版), 2008, 46(9): 898-900.
25. 侯良宝, 王守林, 王清, 等. 超分割放疗同步化疗治疗Ⅲ期非小细胞肺癌. 中国肿瘤临床与康复, 2006, 13(4): 322-324.
26. 高亚丽. 同步和序贯放化疗治疗Ⅲ期非小细胞肺癌的比较分析. 肿瘤基础与临床, 2011, 24(1): 29-31.
27. 房丽, 王红阳, 王玲玲, 等. 放化疗联合治疗局部晚期非小细胞肺癌临床疗效观察. 临床肺科杂志, 2014(7): 1291-1294.
28. 白桦, 侯敏全, 白晓宁. 同步放化疗与序贯化放疗治疗Ⅲ期不能手术非小细胞肺癌的临床疗效. 昆明医科大学学报, 2015, 36(6): 42-45.
29. 石安辉, 朱广迎. 局部晚期非小细胞肺癌放化疗的现状与进展. 临床外科杂志, 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. 任维维, 米登海, 李征, 等. 非小细胞肺癌紫杉醇类联合顺铂同步或序贯放化疗对比的Meta分析. 中华肿瘤防治杂志, 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. 局限期小细胞肺癌同步放化疗与序贯放化疗的Meta分析. 吉林大学, 2014.
39. 王毓洲, 应红艳, 赵林, 等. 局部晚期非小细胞肺癌同步化放疗与序贯化放疗比较的Meta分析. 循证医学, 2007, 7(3): 152-157.

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