Effects of Postoperative Radiotherapy on Survival of Patients With Stage IIIA Resected Non–Small Cell Lung Cancer: Analysis of the SEER Database

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Background: The role of postoperative radiotherapy (PORT) in patients with resected stage IIIA non–small cell lung cancer (NSCLC) remains controversial. The purpose of this study was to explore the effect of PORT on survival of these patients. Methods: Patients aged ≥18 years with stage IIIA NSCLC were identified in the SEER database from 2010 through 2015. Cox regression analysis was used to identify independant prognostic factors in patients with stage IIIA NSCLC. Subgroup analysis of patients stratified by N stage was also performed. Overall survival and lung cancer–related death were compared among the different groups by using Kaplan-Meier analysis and competitive risk analysis. Results: A total of 5,168 patients (1,711 of whom received PORT) were included in the study. In multivariable analysis, PORT was an independent prognostic risk factor for patients with N1 stage (hazard ratio [HR], 1.416, 95% CI, 1.144–1.753; P=.001). PORT was a favorable prognostic factor for patients with stage IIIA, N2 disease with ≥6 positive lymph nodes (HR, 0.742; 95% CI, 0.587–0.938; P=.012). Median survival time of patients with stage IIIA, N2 disease with ≥6 positive lymph nodes who received postoperative chemotherapy combined with PORT was significantly longer compared with those who received postoperative chemotherapy alone (32 vs 25 months, respectively; P=.009). The competitive risk model revealed that 3- and 5-year lung cancer–related mortality rates increased by 8.99% and 16.92%, respectively, in patients with N1 disease who were treated with PORT, whereas the 3-year mortality rate decreased by 4.67% and the 5-year mortality rate by 10.08% in patients with N2 disease and ≥6 positive lymph nodes who were treated using PORT. Conclusions: Our results revealed that PORT significantly improved overall survival and decreased lung cancer–related mortality in patients with stage IIIA, N2 disease with ≥6 positive lymph node metastases. PORT was not recommended for patients with N0 and N1 disease.

Submitted October 29, 2019; accepted for publication January 13, 2020.

Author contributions: Study concept and design: Yang. Data collection and assembly: Gao, Li, Xu. Data analysis and interpretation: Gao, Li. Manuscript preparation: Gao.

Disclosures: The authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Correspondence: GuoWang Yang, MD, Department of Oncology & Hematology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, No. 23 Back Street in the Museum of Art Road, Dongcheng District, Beijing, 100010, China. Email: zyyyzlk@163.com

Supplementary Materials

    • Supplemental Materials (PDF 477.70 KB)
  • 1.

    Tsironis G, Ziogas DC, Kyriazoglou A, . Breakthroughs in the treatment of advanced squamous-cell NSCLC: not the neglected sibling anymore? Ann Transl Med 2018;6:143.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2.

    Veeramachaneni NK, Feins RH, Stephenson BJ, . Management of stage IIIA non-small cell lung cancer by thoracic surgeons in North America. Ann Thorac Surg 2012;94:922926; discussion: 926–928.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Arriagada R, Bergman B, Dunant A, . Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med 2004;350:351360.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Douillard JY, Rosell R, De Lena M, . 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. Lancet Oncol 2006;7:719727.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5.

    Burdett S, Rydzewska L, Tierney JF, . A closer look at the effects of postoperative radiotherapy by stage and nodal status: updated results of an individual participant data meta-analysis in non-small-cell lung cancer. Lung Cancer 2013;80:350352.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6.

    Billiet C, Decaluwé H, Peeters S, . Modern post-operative radiotherapy for stage III non-small cell lung cancer may improve local control and survival: a meta-analysis. Radiother Oncol 2014;110:38.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Kris MG, Gaspar LE, Chaft JE, . Adjuvant systemic therapy and adjuvant radiation therapy for stage I to IIIA completely resected non-small-cell lung cancers: American Society of Clinical Oncology/Cancer Care Ontario clinical practice guideline update. J Clin Oncol 2017;35:29602974.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8.

    PORT Meta-analysis Trialists Group. Postoperative radiotherapy in non-small-cell lung cancer: systematic review and meta-analysis of individual patient data from nine randomised controlled trials. Lancet 1998;352:257263.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Wang K, Eblan MJ, Deal AM, . Cardiac toxicity after radiotherapy for stage III non-small-cell lung cancer: pooled analysis of dose-escalation trials delivering 70 to 90 Gy. J Clin Oncol 2017;35:13871394.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Douillard JY, Rosell R, De Lena M, .. 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. Int J Radiat Oncol Biol Phys 2008;72:695701.

    • Search Google Scholar
    • Export Citation
  • 11.

    Edge SB, Byrd DR, Compton CC, eds. AJCC Cancer Staging Manual, 7th ed. New York, NY: Springer-Verlag; 2009:103–115.

  • 12.

    SEER Site-Specific Surgery of Primary Site Codes SEER Program Code Manual, 3rd Edition, Revision 1. Accessed April 14, 2020. Available at: https://seer.cancer.gov/archive/tools/SEER2003.surg.prim.site.codes.pdf

  • 13.

    Ettinger DS, Wood DE, Aisner DL, . NCCN Guidelines for Non-Small Cell Lung Cancer. Version 3.2020. Accessed April 10, 2020. To view the most recent version, visit NCCN.org.

  • 14.

    Yavuz AA, Topkan E, Onal C, . Prophylactic cranial irradiation in locally advanced non-small cell lung cancer: outcome of recursive partitioning analysis group 1 patients. J Exp Clin Cancer Res 2008;27:80.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    NSCLC Meta-analyses Collaborative Group, Arriagada R, Auperin A, . Adjuvant chemotherapy, with or without postoperative radiotherapy, in operable non-small-cell lung cancer: two meta-analyses of individual patient data. Lancet 2010;375:12671277.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Lally BE, Zelterman D, Colasanto JM, . Postoperative radiotherapy for stage II or III non-small-cell lung cancer using the surveillance, epidemiology, and end results database. J Clin Oncol 2006;24:29983006.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Wisnivesky JP, Halm EA, Bonomi M, . Postoperative radiotherapy for elderly patients with stage III lung cancer. Cancer 2012;118:44784485.

  • 18.

    Zhang H, Zhang DX, Ju T, . The effect of postoperative radiotherapy on the survival of patients with resectable stage III-N2 non-small-cell lung cancer: a systematic review and meta-analysis. Neoplasma 2019;66:717726.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19.

    Morgensztern D, Waqar S, Subramanian J, . Prognostic significance of tumor size in patients with stage III non-small-cell lung cancer: a Surveillance, Epidemiology, and End Results (SEER) survey from 1998 to 2003. J Thorac Oncol 2012;7:14791484.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20.

    Corso CD, Rutter CE, Wilson LD, . 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 Thorac Oncol 2015;10:148155.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21.

    Mikell JL, Gillespie TW, Hall WA, . Postoperative radiotherapy is associated with better survival in non-small cell lung cancer with involved N2 lymph nodes: results of an analysis of the National Cancer Database. J Thorac Oncol 2015;10:462471.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22.

    Robinson CG, Patel AP, Bradley JD, . Postoperative radiotherapy for pathologic N2 non-small-cell lung cancer treated with adjuvant chemotherapy: a review of the National Cancer Data Base. J Clin Oncol 2015;33:870876.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23.

    Yuan C, Tao X, Zheng D, . The lymph node status and histologic subtypes influenced the effect of postoperative radiotherapy on patients with N2 positive IIIA non-small cell lung cancer. J Surg Oncol 2019;119:379387.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24.

    Asamura H, Chansky K, Crowley J, . The International Association for the Study of Lung Cancer Lung Cancer Staging Project: proposals for the revision of the N descriptors in the forthcoming 8th edition of the TNM classification for lung cancer. J Thorac Oncol 2015;10:16751684.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25.

    Katsumata S, Aokage K, Ishii G, . Prognostic impact of the number of metastatic lymph nodes on the eighth edition of the TNM classification of NSCLC. J Thorac Oncol 2019;14:14081418.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26.

    Herskovic A, Mauer E, Christos P, . Role of postoperative radiotherapy in pathologic stage IIIA (N2) non-small cell lung cancer in a prospective nationwide oncology outcomes database. J Thorac Oncol 2017;12:302313.

    • Crossref
    • Search Google Scholar
    • Export Citation
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