Abstract：Non‐small cell lung cancer(NSCLC) is highly malignant and has poor prognosis, in which stage ⅢA(N2) NSCLC approximately accounts for 20%. Patients with stage ⅢA(N2) NSCLC have high heterogeneity and distinct survival difference. Loco‐regional recurrence and distant metastasis are the main causes of treatment failure. At present, whether stage ⅢA(N2) NSCLC patients should receive postoperative radiotherapy(PORT) remains controversial. Such patients still lack high level proof to receive PORT.
Ling Lixian,Fu Jianfei. Research progress on efficacy and influencing factors of postoperative radiotherapy for stage ⅢA(N2) non‐small cell lung cancer[J]. Chinese Journal of Radiation Oncology, 2022, 31(10): 944-948.
[1] Arriagada R, Auperin A, Burdett S, et al.Adjuvant chemotherapy, with or without postoperative radiotherapy, in operable non-small-cell lung cancer: two meta-analyses of individual patient data[J]. Lancet, 2010,375(9722):1267-1277. DOI: 10.1016/S0140-6736(10)60059-1. [2] Douillard JY, Rosell R, De Lena M, et al.Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial[J]. Lancet Oncol, 2006,7(9):719-727. DOI: 10.1016/S1470-2045(06)70804-X. [3] Lally BE, Zelterman D, Colasanto JM, et al.Postoperative radiotherapy for stage II or III non-small-cell lung cancer using the surveillance, epidemiology, and end results database[J]. J Clin Oncol, 2006,24(19):2998-3006. DOI: 10.1200/JCO.2005.04.6110. [4] Douillard JY, Rosell R, De Lena M, et al.Impact of postoperative radiation therapy on survival in patients with complete resection and stage I, II, or IIIA non-small-cell lung cancer treated with adjuvant chemotherapy: the adjuvant Navelbine International Trialist Association (ANITA) Randomized Trial[J]. Int J Radiat Oncol Biol Phys, 2008,72(3):695-701. DOI: 10.1016/j.ijrobp.2008.01.044. [5] Robinson CG, Patel AP, Bradley JD, et al.Postoperative radiotherapy for pathologic N2 non-small-cell lung cancer treated with adjuvant chemotherapy: a review of the National Cancer Data Base[J]. J Clin Oncol, 2015,33(8):870-876. DOI: 10.1200/JCO.2014.58.5380. [6] Corso CD, Rutter CE, Wilson LD, et al.Re-evaluation of the role of postoperative radiotherapy and the impact of radiation dose for non-small-cell lung cancer using the National Cancer Database[J]. J Thorac Oncol, 2015,10(1):148-155. DOI: 10.1097/JTO.0000000000000406. [7] Breen WG, Merrell KW, Mansfield AS, et al.Predictors of relapse and evaluation of the role of postoperative radiation therapy in a modern series of patients with surgically resected stage III (N2) non-small cell lung cancer[J]. Adv Radiat Oncol, 2017,2(1):12-18. DOI: 10.1016/j.adro.2016.12.004. [8] Shen WY, Ji J, Zuo YS, et al.Comparison of efficacy for postoperative chemotherapy and concurrent radiochemotherapy in patients with IIIA-pN2 non-small cell lung cancer: an early closed randomized controlled trial[J]. Radiother Oncol, 2014,110(1):120-125. DOI: 10.1016/j.radonc.2013.10.008. [9] Brandt WS, Yan W, Leeman JE, et al.Postoperative radiotherapy for surgically resected ypn2 non-small cell lung cancer[J]. Ann Thorac Surg, 2018,106(3):848-855. DOI: 10.1016/j.athoracsur.2018.04.064. [10] Hsu HC, Wang CJ, Huang EY, et al.Post-operative adjuvant thoracic radiotherapy for patients with completely resected non-small cell lung cancer with nodal involvement: outcome and prognostic factors[J]. Br J Radiol, 2004,77(913):43-48. DOI: 10.1259/bjr/21845347. [11] 杜芳芳, 袁智勇, 王军, 等. 术后放射治疗在PN2期非小细胞肺癌中的地位[J].中国肺癌杂志,2009,12(11):1164-1168. DOI: 10.3779/j.issn.1009-3419.2009.11.07 Du FF, Yuan ZY, Wang J,et al.The role of postoperative radiotherapy on stage N2 non‐small cell lung cancer[J]. Chinese Journal of Lung Cancer, ,2009,12(11):1164-1168. DOI: 10.3779/j.issn.1009-3419.2009.11.07 [12] Saito M, Kato H.Prognostic factors in patients with pathological and N2 non-small cell lung cancer[J]. Ann Thorac Cardiovasc Surg, 2008,14(1):1-2. [13] Hui Z, Dai H, Liang J, et al.Selection of proper candidates with resected pathological stage IIIA-N2 non-small cell lung cancer for postoperative radiotherapy[J]. Thorac Cancer, 2015,6(3):346-353. DOI: 10.1111/1759-7714.12186. [14] Ding X, Hui Z, Dai H, et al.A proposal for combination of lymph node ratio and anatomic location of involved lymph nodes for nodal classification in non-small cell lung cancer[J]. J Thorac Oncol, 2016,11(9):1565-1573. DOI: 10.1016/j.jtho.2016.05.004. [15] Fan Y, Du Y, Sun W, et al.Including positive lymph node count in the AJCC N staging may be a better predictor of the prognosis of NSCLC patients, especially stage III patients: a large population-based study[J]. Int J Clin Oncol, 2019,24(11):1359-1366. DOI: 10.1007/s10147-019-01483-1. [16] 陈建武, 张幸平, 曾奕明, 等. Ⅲa(N_2)期非小细胞肺癌术后放疗疗效分析[J].重庆医科大学学报,2009,34(11):1566-1570. Chen JW, Zhang XP, Zeng YM, et al.An analysis of postoperative radiotherapy for patients with completely resected stage Ⅲ a( N_2) non-small cell lung cancer[J].Journal of Chongqing Medical University,2009,34(11):1566-1570. [17] Kim BH, Kim HJ, Wu HG, et al.Role of postoperative radiotherapy after curative resection and adjuvant chemotherapy for patients with pathological stage N2 non-small-cell lung cancer: a propensity score matching analysis[J]. Clin Lung Cancer, 2014,15(5):356-364. DOI: 10.1016/j.cllc.2014.05.005. [18] Liu T, Mu Y, Dang J, et al.The role of postoperative radiotherapy for completely resected pIIIA-N2 non-small cell lung cancer patients with different clinicopathological features: a systemic review and meta-analysis[J]. J Cancer, 2019,10(17):3941-3949. DOI: 10.7150/jca.28680. [19] Aokage K, Yoshida J, Ishii G, et al.Subcarinal lymph node in upper lobe non-small cell lung cancer patients: is selective lymph node dissection valid?[J]. Lung Cancer, 2010,70(2):163-167. DOI: 10.1016/j.lungcan.2010.02.009. [20] 刘敬伟, 李简, 林钢, 等. ⅢA-N2期非小细胞肺癌根治性切除术后的复发分析[J].中华医学杂志,2012(33):2314-2318. Liu JW, Li J, Lin G, et al.Analysis of recurrence patterns after curative resection of stage IIIA‐N2 non‐small cell lung cancer[J]. National Medical Journal of China,2012(33):2314-2318. [21] 韩玮. ⅢA‐N2期非小细胞肺癌术后化疗后失败模式及术后放疗的价值[D]. 石家庄:河北医科大学, 2016. Han W.The failure patterns and the significance of radiotherapy after resection and adjuvant chemotherapy for stage IIIA‐N2 non‐small cell lung cancer[D]. Shijiazhuang: Hebei Medical University, 2016. [22] Zhang S, Wang L, Lu F, et al.[Correlation between lymph node ratio and clinicopathological features and prognosis of IIIa-N2 non-small cell lung cancer][J]. Zhongguo Fei Ai Za Zhi, 2019,22(11):702-708. DOI: 10.3779/j.issn.1009-3419.2019.11.04. [23] Zeng WQ, Feng W, Xie L, et al.Postoperative radiotherapy for resected stage IIIA-N2 non-small-cell lung cancer: a population-based time-trend study[J]. Lung, 2019,197(6):741-751. DOI: 10.1007/s00408-019-00284-7. [24] Urban D, Bar J, Solomon B, et al.Lymph node ratio may predict the benefit of postoperative radiotherapy in non-small-cell lung cancer[J]. J Thorac Oncol, 2013,8(7):940-946. DOI: 10.1097/JTO.0b013e318292c53e. [25] Shinde A, Horne ZD, Li R, et al.Optimal adjuvant therapy in clinically N2 non-small cell lung cancer patients undergoing neoadjuvant chemotherapy and surgery: The importance of pathological response and lymph node ratio[J]. Lung Cancer, 2019,133:136-143. DOI: 10.1016/j.lungcan.2019.05.020. [26] McAleese J, Taylor A, Walls GM, et al. Differential relapse patterns for non-small cell lung cancer subtypes adenocarcinoma and squamous cell carcinoma: implications for radiation oncology[J]. Clin Oncol (R Coll Radiol), 2019,31(10):711-719. DOI: 10.1016/j.clon.2019.07.008. [27] Varlotto JM, Yao AN, DeCamp MM, et al. Nodal stage of surgically resected non-small cell lung cancer and its effect on recurrence patterns and overall survival[J]. Int J Radiat Oncol Biol Phys, 2015,91(4):765-773. DOI: 10.1016/j.ijrobp.2014. 12.028. [28] 秦培艳, 袁智勇, 王军, 等. IIIA(N2)期非小细胞肺癌术后失败模式分析[J].中国肺癌杂志,2009,12(10):1095-1100. DOI: 10.3779/j.issn.1009-3419.2009.10.08. Qin PY, Yuan ZY, Wang J, et al.Research on postoperative radiotherapy for non-small cell lung cancer of stage IIIA(N2) according to the failure patterns after pulmonary resection[J].Chinese Journal of Lung Cancer,2009,12(10):1095-1100. DOI: 10.3779/j.issn.1009-3419.2009.10.08. [29] 田文泽, 万里, 胡忠吾, 等. 术后辅助放疗对N2期非小细胞肺癌患者预后的影响[J].中华放射医学与防护杂志,2020,40(7):507-511. DOI: 10.3760/cma.j.issn.0254-5098.2020. 07.003. Tian WZ, Wang L, Hu ZW, et al.The effect of adjuvant radiotherapy on N2 patients with non-small cell lung cancer[J].Chin J Radio Med Prot,2020,40(7):507-511. DOI: 10.3760/cma.j.issn.0254-5098.2020.07.003. [30] 戴洪海. 根治性切除ⅢA期‐N2非小细胞肺癌的术后放疗[D].中国协和医科大学, 2009. Dai HH.Effect of PORT for completely resceted stage ⅢA‐N2 non-small cell lung cancer[J]. Peking Union Medical College, 2009. [31] Koukourakis M, Hlouverakis G, Kosma L, et al.The impact of overall treatment time on the results of radiotherapy for nonsmall cell lung carcinoma[J]. Int J Radiat Oncol Biol Phys, 1996,34(2):315-322. DOI: 10.1016/0360-3016(95)02102-7. [32] 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[J]. Oncotarget, 2017,8(38):62998-63013. DOI: 10.18632/oncotarget.18071. [33] McMillan MT, Ojerholm E, Verma V, et al. Radiation treatment time and overall survival in locally advanced non-small cell lung cancer[J]. Int J Radiat Oncol Biol Phys, 2017,98(5):1142-1152. DOI: 10.1016/j.ijrobp.2017.04.004. [34] Sura K, Grills IS, Vu CC, et al.Improved survival with increased time-to-radiation and sequential chemotherapy after surgery for pn2 non-small-cell lung cancer[J]. Clin Lung Cancer, 2018,19(2):e185-e194. DOI: 10.1016/j.cllc.2017. 10.011. [35] Francis S, Orton A, Stoddard G, et al.Sequencing of postoperative radiotherapy and chemotherapy for locally advanced or incompletely resected non-small-cell lung cancer[J]. J Clin Oncol, 2018,36(4):333-341. DOI: 10.1200/JCO.2017.74.4771. [36] Postoperative radiotherapy in non-small-cell lung cancer: systematic review and meta-analysis of individual patient data from nine randomised controlled trials. PORT Meta-analysis Trialists Group[J]. Lancet, 1998,352(9124):257-263. [37] Wakelee HA, Stephenson P, Keller SM, et al.Post-operative radiotherapy (PORT) or chemoradiotherapy (CPORT) following resection of stages II and IIIA non-small cell lung cancer (NSCLC) does not increase the expected risk of death from intercurrent disease (DID) in Eastern Cooperative Oncology Group (ECOG) trial E3590[J]. Lung Cancer, 2005,48(3):389-397. DOI: 10.1016/j.lungcan.2004.11.007. [38] Kepka L, Bujko K, Orlowski TM, et al.Cardiopulmonary morbidity and quality of life in non-small cell lung cancer patients treated with or without postoperative radiotherapy[J]. Radiother Oncol, 2011,98(2):238-243. DOI: 10.1016/j.radonc.2010.09.020. [39] Lally BE, Detterbeck FC, Geiger AM, et al.The risk of death from heart disease in patients with nonsmall cell lung cancer who receive postoperative radiotherapy: analysis of the Surveillance, Epidemiology, and End Results database[J]. Cancer, 2007,110(4):911-917. DOI: 10.1002/cncr.22845. [40] Feng W, Zhang Q, Fu XL, et al.The emerging outcome of postoperative radiotherapy for stage IIIA(N2) non-small cell lung cancer patients: based on the three-dimensional conformal radiotherapy technique and institutional standard clinical target volume[J]. BMC Cancer, 2015,15:348. DOI: 10.1186/s12885-015-1326-6.
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