Effect of postoperative radiotherapy after complete resection in patients with stage ⅢA-N2 non-small cell lung cancer: A propensity score matching analysis_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

XU Zhengshui ¹ , ZHU Minxia ¹ , JIANG Jiantao ¹ , LIU Shiyuan ¹ , CHEN Jia ² , ZHANG Danjie ¹ , LI Jianzhong ¹ , SUN Liangzhang ¹ ,  LI Shaomin ¹

1. Department of Thoracic Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi’an, 710004, P. R. China;
2. Department of Cardiovascular Surgery, Xijing Hospital, Air Force Medical University, Xi’an, 710032, P. R. China;

Corresponding author：

LI Shaomin, Email: lism51487@xjtu.edu.cn

Keywords：

Non-small cell lung cancer; postoperative radiotherapy; complete resection; chemotherapy; propensity score matching analysis

DOI：

10.7507/1007-4848.202304069

Video：

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Objective To evaluate the value of postoperative radiotherapy (PORT) in patients with stage ⅢA-N2 non-small cell lung cancer who received complete resection and chemotherapy. Methods Patients with stage ⅢA-N2 non-small cell lung cancer who received complete resection and chemotherapy were chosen from the SEER Research Plus Database [17 Registries, November 2012 Submission (2000-2019)]. The patients were divided into a PORT group and a non-PORT group according to whether the PORT was used. To balance baseline characteristics between non-PORT and PORT groups, R software was used to conduct a propensity score matching (PSM) with a ratio of 1 : 1 and a matching tolerance of 0.01. Both the Cox regression analysis and Kaplan-Meier survival analysis were conducted to evaluate the value of PORT in terms of overall survival (OS) and disease-specific survival (DSS). Results In total, 2468 patients with stage ⅢA-N2 non-small cell lung cancer were enrolled, including 1078 males and 1390 females with a median age of 65 (58-71) years. There were 1336 patients in the PORT group, and 1132 patients in the non-PORT group. Cox regression analysis showed that PORT was not significantly associated with OS (multivariate analysis: HR=1.051, 95%CI 0.949-1.164, P=0.338) and DSS (multivariate analysis: HR=1.094, 95%CI 0.976-1.225, P=0.123). No statistical difference was found in the OS or DSS between non-PORT group and PORT group after PSM analysis (P＞0.05). Conclusion PORT does not have a survival benefit for patients with stage ⅢA-N2 non-small cell lung cancer who received complete resection and chemotherapy.

Citation： XU Zhengshui, ZHU Minxia, JIANG Jiantao, LIU Shiyuan, CHEN Jia, ZHANG Danjie, LI Jianzhong, SUN Liangzhang, LI Shaomin. Effect of postoperative radiotherapy after complete resection in patients with stage ⅢA-N2 non-small cell lung cancer: A propensity score matching analysis. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2025, 32(7): 1006-1012. doi: 10.7507/1007-4848.202304069 Copy

1.	Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2024, 74(3): 229-263.
2.	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.
3.	Le Pechoux C, Pourel N, Barlesi F, et al. Postoperative radiotherapy versus no postoperative radiotherapy in patients with completely resected non-small-cell lung cancer and proven mediastinal N2 involvement (Lung ART): An open-label, randomised, phase 3 trial. Lancet Oncol, 2022, 23(1): 104-114.
4.	Zhu L, Xia B, Ma S. Postoperative radiotherapy for patients with completely resected stageⅢA-N2 non-small cell lung cancer: Opt-in or opt-out. Thorac Cancer, 2022, 13(5): 659-663.
5.	Lin SM, Ku HY, Hsu CY, et al. Long-term survival effect of the interval between postoperative chemotherapy and radiotherapy in patients with completely resected pathological N2 non-small-cell lung cancer. Cancers (Basel), 2021, 13(10): 2494.
6.	Sinn K, Mosleh B, Steindl A, et al. Neoadjuvant chemoradiotherapy is superior to chemotherapy alone in surgically treated stage Ⅲ/N2 non-small-cell lung cancer: A retrospective single-center cohort study. ESMO Open, 2022, 7(2): 100466.
7.	Hui Z, Men Y, Hu C, et al. Effect of postoperative radiotherapy for patients with pⅢa-N2 non-small cell lung cancer after complete resection and adjuvant chemotherapy: The phase 3 PORT-C randomized clinical trial. JAMA Oncol, 2021, 7(8): 1178-1185.
8.	Faivre-Finn C, Edwards JG, Hatton M. Postoperative radiation therapy should not be used for the therapy of stageⅢ-N2 NSCLC. J Thorac Oncol, 2022, 17(2): 197-199.
9.	Liu J, Ladbury C, Kim J, et al. Postoperative radiation therapy should be used for completely resected stageⅢ-N2 NSCLC in select patients. J Thorac Oncol, 2022, 17(2): 194-196.
10.	Pang Z, Yang Y, Ding N, et al. Optimal managements of stageⅢA (N2) non-small cell lung cancer patients: A population-based survival analysis. J Thorac Dis, 2017, 9(10): 4046-4056.
11.	Wang Y, Cao Y, Wu M, et al. Effect of preoperative radiotherapy on overall survival in N2 non-small-cell lung cancer: A propensity score-matched analysis of Surveillance, Epidemiology, and End Results database. Interact Cardiovasc Thorac Surg, 2022, 35(1): ivab321.
12.	Zhang H, Zhang DX, Ju T, et al. The effect of postoperative radiotherapy on the survival of patients with resectable stageⅢ-N2 non-small-cell lung cancer: A systematic review and meta-analysis. Neoplasma, 2019, 66(5): 717-726.
13.	Sakib N, Li N, Zhu X, et al. Effect of postoperative radiotherapy on outcome in resectable stageⅢA-N2 non-small-cell lung cancer: An updated meta-analysis. Nucl Med Commun, 2018, 39(1): 51-59.
14.	Wang SF, Mao NQ, Zhao WH, et al. Postoperative radiotherapy in pⅢA-N2 non-small cell lung cancer after complete resection and adjuvant chemotherapy: A meta-analysis. Medicine (Baltimore), 2022, 101(28): e29550.
15.	Lei T, Li J, Zhong H, et al. Postoperative radiotherapy for patients with resectable stage Ⅲ-N2 non-small cell lung cancer: A systematic review and meta-analysis. Front Oncol, 2021, 11: 680615.
16.	Yamasaki N, Kim YH, Iwatsubo S, et al. Role of postoperative radiotherapy in patients with completely resected pⅢA-N2 non-small cell lung cancer. Clin Lung Cancer, 2022, 23(3): e171-e172.
17.	Sun X, Men Y, Wang J, et al. Risk of cardiac-related mortality in stageⅢA-N2 non-small cell lung cancer: Analysis of the Surveillance, Epidemiology, and End Results (SEER) database. Thorac Cancer, 2021, 12(9): 1358-1365.
18.	Wang X, Song J, Long J, et al. Effects of postoperative radiotherapy on cardiovascular-pulmonary disease mortality in patients with stageⅢA-N2 resected NSCLC: Analysis of the SEER database. Radiat Oncol, 2021, 16(1): 184.
19.	Duan H, Liang L, Xie S, et al. The impact of order with radiation therapy in stageⅢA pathologic N2 NSCLC patients: A population-based study. BMC Cancer, 2020, 20(1): 809.
20.	Gao F, Li N, Xu Y, et al. Evaluation of postoperative radiotherapy effect on survival of resected stageⅢ-N2 non-small cell lung cancer patients. Front Oncol, 2020, 10: 1135.
21.	Wang S, Ma Z, Yang X, et al. Choice of postoperative radiation for stageⅢA pathologic N2 non-small cell lung cancer: Impact of metastatic lymph node number. Radiat Oncol, 2017, 12(1): 207.
22.	Zarinshenas R, Ladbury C, McGee H, et al. Machine learning to refine prognostic and predictive nodal burden thresholds for post-operative radiotherapy in completely resected stageⅢ-N2 non-small cell lung cancer. Radiother Oncol, 2022, 173: 10-18.
23.	Allaeys T, Berzenji L, Lauwers P, et al. Multimodality treatment including surgery related to the type of N2 involvement in locally advanced non-small cell lung cancer. Cancers (Basel), 2022, 14(7): 1656.
24.	Zhang CC, Hou RP, Xia WY, et al. Prognostic index for estimating the survival benefit of postoperative radiotherapy in pathologic N2 non-small cell lung cancer: A real-world validation study. Lung Cancer, 2021, 156: 100-108.
25.	Zeng WQ, Feng W, Xie L, et al. Postoperative radiotherapy for resected stageⅢA-N2 non-small-cell lung cancer: A population-based time-trend study. Lung, 2019, 197(6): 741-751.
26.	Zhang CC, Yu W, Zhang Q, et al. A decision support framework for postoperative radiotherapy in patients with pathological N2 non-small cell lung cancer. Radiother Oncol, 2022, 173: 313-318.
27.	Xu L, Xie HN, Chen XK, et al. Patient prognostic scores and association with survival improvement offered by postoperative radiotherapy for resectedⅢA/N2 non-small cell lung cancer: A population-based study. Thorac Cancer, 2021, 12(6): 760-767.

1. Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2024, 74(3): 229-263.
2. 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.
3. Le Pechoux C, Pourel N, Barlesi F, et al. Postoperative radiotherapy versus no postoperative radiotherapy in patients with completely resected non-small-cell lung cancer and proven mediastinal N2 involvement (Lung ART): An open-label, randomised, phase 3 trial. Lancet Oncol, 2022, 23(1): 104-114.
4. Zhu L, Xia B, Ma S. Postoperative radiotherapy for patients with completely resected stageⅢA-N2 non-small cell lung cancer: Opt-in or opt-out. Thorac Cancer, 2022, 13(5): 659-663.
5. Lin SM, Ku HY, Hsu CY, et al. Long-term survival effect of the interval between postoperative chemotherapy and radiotherapy in patients with completely resected pathological N2 non-small-cell lung cancer. Cancers (Basel), 2021, 13(10): 2494.
6. Sinn K, Mosleh B, Steindl A, et al. Neoadjuvant chemoradiotherapy is superior to chemotherapy alone in surgically treated stage Ⅲ/N2 non-small-cell lung cancer: A retrospective single-center cohort study. ESMO Open, 2022, 7(2): 100466.
7. Hui Z, Men Y, Hu C, et al. Effect of postoperative radiotherapy for patients with pⅢa-N2 non-small cell lung cancer after complete resection and adjuvant chemotherapy: The phase 3 PORT-C randomized clinical trial. JAMA Oncol, 2021, 7(8): 1178-1185.
8. Faivre-Finn C, Edwards JG, Hatton M. Postoperative radiation therapy should not be used for the therapy of stageⅢ-N2 NSCLC. J Thorac Oncol, 2022, 17(2): 197-199.
9. Liu J, Ladbury C, Kim J, et al. Postoperative radiation therapy should be used for completely resected stageⅢ-N2 NSCLC in select patients. J Thorac Oncol, 2022, 17(2): 194-196.
10. Pang Z, Yang Y, Ding N, et al. Optimal managements of stageⅢA (N2) non-small cell lung cancer patients: A population-based survival analysis. J Thorac Dis, 2017, 9(10): 4046-4056.
11. Wang Y, Cao Y, Wu M, et al. Effect of preoperative radiotherapy on overall survival in N2 non-small-cell lung cancer: A propensity score-matched analysis of Surveillance, Epidemiology, and End Results database. Interact Cardiovasc Thorac Surg, 2022, 35(1): ivab321.
12. Zhang H, Zhang DX, Ju T, et al. The effect of postoperative radiotherapy on the survival of patients with resectable stageⅢ-N2 non-small-cell lung cancer: A systematic review and meta-analysis. Neoplasma, 2019, 66(5): 717-726.
13. Sakib N, Li N, Zhu X, et al. Effect of postoperative radiotherapy on outcome in resectable stageⅢA-N2 non-small-cell lung cancer: An updated meta-analysis. Nucl Med Commun, 2018, 39(1): 51-59.
14. Wang SF, Mao NQ, Zhao WH, et al. Postoperative radiotherapy in pⅢA-N2 non-small cell lung cancer after complete resection and adjuvant chemotherapy: A meta-analysis. Medicine (Baltimore), 2022, 101(28): e29550.
15. Lei T, Li J, Zhong H, et al. Postoperative radiotherapy for patients with resectable stage Ⅲ-N2 non-small cell lung cancer: A systematic review and meta-analysis. Front Oncol, 2021, 11: 680615.
16. Yamasaki N, Kim YH, Iwatsubo S, et al. Role of postoperative radiotherapy in patients with completely resected pⅢA-N2 non-small cell lung cancer. Clin Lung Cancer, 2022, 23(3): e171-e172.
17. Sun X, Men Y, Wang J, et al. Risk of cardiac-related mortality in stageⅢA-N2 non-small cell lung cancer: Analysis of the Surveillance, Epidemiology, and End Results (SEER) database. Thorac Cancer, 2021, 12(9): 1358-1365.
18. Wang X, Song J, Long J, et al. Effects of postoperative radiotherapy on cardiovascular-pulmonary disease mortality in patients with stageⅢA-N2 resected NSCLC: Analysis of the SEER database. Radiat Oncol, 2021, 16(1): 184.
19. Duan H, Liang L, Xie S, et al. The impact of order with radiation therapy in stageⅢA pathologic N2 NSCLC patients: A population-based study. BMC Cancer, 2020, 20(1): 809.
20. Gao F, Li N, Xu Y, et al. Evaluation of postoperative radiotherapy effect on survival of resected stageⅢ-N2 non-small cell lung cancer patients. Front Oncol, 2020, 10: 1135.
21. Wang S, Ma Z, Yang X, et al. Choice of postoperative radiation for stageⅢA pathologic N2 non-small cell lung cancer: Impact of metastatic lymph node number. Radiat Oncol, 2017, 12(1): 207.
22. Zarinshenas R, Ladbury C, McGee H, et al. Machine learning to refine prognostic and predictive nodal burden thresholds for post-operative radiotherapy in completely resected stageⅢ-N2 non-small cell lung cancer. Radiother Oncol, 2022, 173: 10-18.
23. Allaeys T, Berzenji L, Lauwers P, et al. Multimodality treatment including surgery related to the type of N2 involvement in locally advanced non-small cell lung cancer. Cancers (Basel), 2022, 14(7): 1656.
24. Zhang CC, Hou RP, Xia WY, et al. Prognostic index for estimating the survival benefit of postoperative radiotherapy in pathologic N2 non-small cell lung cancer: A real-world validation study. Lung Cancer, 2021, 156: 100-108.
25. Zeng WQ, Feng W, Xie L, et al. Postoperative radiotherapy for resected stageⅢA-N2 non-small-cell lung cancer: A population-based time-trend study. Lung, 2019, 197(6): 741-751.
26. Zhang CC, Yu W, Zhang Q, et al. A decision support framework for postoperative radiotherapy in patients with pathological N2 non-small cell lung cancer. Radiother Oncol, 2022, 173: 313-318.
27. Xu L, Xie HN, Chen XK, et al. Patient prognostic scores and association with survival improvement offered by postoperative radiotherapy for resectedⅢA/N2 non-small cell lung cancer: A population-based study. Thorac Cancer, 2021, 12(6): 760-767.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Effect of postoperative radiotherapy after complete resection in patients with stage ⅢA-N2 non-small cell lung cancer: A propensity score matching analysis

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