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 2021Submission (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.

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.

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