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Published in: BMC Cancer 1/2015

Open Access 01-12-2015 | Research article

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

Authors: Wen Feng, Qin Zhang, Xiao-Long Fu, Xu-Wei Cai, Zheng-Fei Zhu, Huan-Jun Yang, Jia-Qing Xiang, Ya-Wei Zhang, Hai-Quan Chen

Published in: BMC Cancer | Issue 1/2015

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Abstract

Background

The aim of this study was to evaluate the clinical efficacy of postoperative radiotherapy (PORT), administered using three-dimensional conformal radiotherapy (3D-CRT) and our institutional standard clinical target volume (CTV) delineation, for completely resected stage IIIA(N2) non-small cell lung cancer (NSCLC).

Methods

From 2005 to 2012, consecutive patients with pT1-3N2 NSCLC who were treated with PORT employing our institutional CTV delineation after complete surgery or who underwent complete resection in our hospital but without PORT were identified. We excluded patients who had received neoadjuvant chemotherapy or radiation therapy (RT). Kaplan-Meier estimates for locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS) and overall survival (OS) were performed. In the OS estimation, patients who received epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) during follow-up were censored at the time of TKI initiation.

Results

Data from 70 patients in the PORT group and 287 in the non-PORT group were analysed. All 70 cases received 3D-CRT following our institutional CTV guideline, with a median total dose of 50.4 Gy at 1.8 Gy/fraction. At a median follow-up of 34.3 months for the PORT group and 31.2 months for the non-PORT group, PORT significantly improved local control (5-yr LRFS 91.9% for PORT vs 66.4% for non-PORT, P < 0.001) and OS (5-yr OS 57.5% for PORT vs 35.1% for non-PORT, P = 0.003), whereas no differences in DMFS were noted (P = 0.18). In multivariable analyses, PORT was independently associated with an improved LRFS (HR 0.2, P = 0.001) and OS (HR 0.4, P = 0.001). All patients completed the planned RT dose without interruption of RT due to treatment-related complications.

Conclusions

Our data suggested that PORT administered using the 3D-CRT technique following our institutional CTV delineation guideline resulted in a promising outcome with favourable survival for completely resected IIIA(N2) NSCLC, after controlling for subsequent EGFR-TKI confounding in the OS analysis. Prospective trials are needed to further corroborate these results.
Literature
1.
go back to reference Andre F, Grunenwald D, Pignon JP, Dujon A, Pujol JL, Brichon PY, et al. Survival of patients with resected N2 non-small-cell lung cancer: evidence for subclassification and implications. J Clin Oncol. 2000;18:2981–9.PubMed Andre F, Grunenwald D, Pignon JP, Dujon A, Pujol JL, Brichon PY, et al. Survival of patients with resected N2 non-small-cell lung cancer: evidence for subclassification and implications. J Clin Oncol. 2000;18:2981–9.PubMed
2.
go back to reference Spira A, Ettinger DS. Multidisciplinary management of lung cancer. N Engl J Med. 2004;350:379–92.CrossRefPubMed Spira A, Ettinger DS. Multidisciplinary management of lung cancer. N Engl J Med. 2004;350:379–92.CrossRefPubMed
3.
go back to reference NSCLC Meta-analyses Collaborative Group, Arriagada R, Auperin A, Burdett S, Higgins JP, Johnson DH, et al. Adjuvant chemotherapy, with or without postoperative radiotherapy, in operable non-small-cell lung cancer: two meta-analyses of individual patient data. Lancet. 2010;375:1267–77.CrossRefPubMedCentral NSCLC Meta-analyses Collaborative Group, Arriagada R, Auperin A, Burdett S, Higgins JP, Johnson DH, et al. Adjuvant chemotherapy, with or without postoperative radiotherapy, in operable non-small-cell lung cancer: two meta-analyses of individual patient data. Lancet. 2010;375:1267–77.CrossRefPubMedCentral
4.
go back to reference 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;352:257–63.CrossRef 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;352:257–63.CrossRef
5.
go back to reference PORT Meta-analysis Trialists Group. Postoperative radiotherapy for non-small cell lung cancer. Cochrane Database Syst Rev. 2005;2:CD002142. PORT Meta-analysis Trialists Group. Postoperative radiotherapy for non-small cell lung cancer. Cochrane Database Syst Rev. 2005;2:CD002142.
6.
go back to reference Burdett S, Rydzewska L, Tierney JF, Fisher DJ. 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;80:350–2.CrossRefPubMed Burdett S, Rydzewska L, Tierney JF, Fisher DJ. 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;80:350–2.CrossRefPubMed
7.
go back to reference Lally BE, Zelterman D, Colasanto JM, Haffty BG, Detterbeck FC, Wilson LD. Postoperative radiotherapy for stage II or III non-small-cell lung cancer using the surveillance, epidemiology, and end results database. J Clin Oncol. 2006;24:2998–3006.CrossRefPubMed Lally BE, Zelterman D, Colasanto JM, Haffty BG, Detterbeck FC, Wilson LD. Postoperative radiotherapy for stage II or III non-small-cell lung cancer using the surveillance, epidemiology, and end results database. J Clin Oncol. 2006;24:2998–3006.CrossRefPubMed
8.
go back to reference Douillard JY, Rosell R, De Lena M, Riggi M, Hurteloup P, Mahe MA. 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;72:695–701.CrossRefPubMed Douillard JY, Rosell R, De Lena M, Riggi M, Hurteloup P, Mahe MA. 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;72:695–701.CrossRefPubMed
9.
go back to reference Zou B, Xu Y, Li T, Li W, Tang B, Zhou L, et al. A multicenter retrospective analysis of survival outcome following postoperative chemoradiotherapy in non-small-cell lung cancer patients with N2 nodal disease. Int J Radiat Oncol Biol Phys. 2010;77:321–8.CrossRefPubMed Zou B, Xu Y, Li T, Li W, Tang B, Zhou L, et al. A multicenter retrospective analysis of survival outcome following postoperative chemoradiotherapy in non-small-cell lung cancer patients with N2 nodal disease. Int J Radiat Oncol Biol Phys. 2010;77:321–8.CrossRefPubMed
10.
go back to reference Scotti V, Meattini I, Saieva C, Agresti B, de Luca CC, Bastiani P, et al. Post-operative radiotherapy in N2 non-small cell lung cancer: a retrospective analysis of 175 patients. Radiother Oncol. 2010;96:84–8.CrossRefPubMed Scotti V, Meattini I, Saieva C, Agresti B, de Luca CC, Bastiani P, et al. Post-operative radiotherapy in N2 non-small cell lung cancer: a retrospective analysis of 175 patients. Radiother Oncol. 2010;96:84–8.CrossRefPubMed
11.
go back to reference Dai H, Hui Z, Ji W, Liang J, Lu J, Ou G, et al. Postoperative radiotherapy for resected pathological stage IIIA-N2 non-small cell lung cancer: a retrospective study of 221 cases from a single institution. Oncologist. 2011;16:641–50.CrossRefPubMedPubMedCentral Dai H, Hui Z, Ji W, Liang J, Lu J, Ou G, et al. Postoperative radiotherapy for resected pathological stage IIIA-N2 non-small cell lung cancer: a retrospective study of 221 cases from a single institution. Oncologist. 2011;16:641–50.CrossRefPubMedPubMedCentral
12.
go back to reference Mantovani C, Levra NG, Filippi AR, Novello S, Buffoni L, Ragona R, et al. Postoperative radiotherapy for patients with completely resected pathologic N2 non-small-cell lung cancer: a retrospective analysis. Clin Lung Cancer. 2013;14:194–9.CrossRefPubMed Mantovani C, Levra NG, Filippi AR, Novello S, Buffoni L, Ragona R, et al. Postoperative radiotherapy for patients with completely resected pathologic N2 non-small-cell lung cancer: a retrospective analysis. Clin Lung Cancer. 2013;14:194–9.CrossRefPubMed
13.
go back to reference Shen WY, Ji J, Zuo YS, Pu J, Xu YM, Zong CD, 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. Radiother Oncol. 2014;110:120–5.CrossRefPubMed Shen WY, Ji J, Zuo YS, Pu J, Xu YM, Zong CD, 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. Radiother Oncol. 2014;110:120–5.CrossRefPubMed
14.
go back to reference Miles EF, Kelsey CR, Kirkpatrick JP, Marks LB. Estimating the magnitude and field-size dependence of radiotherapy-induced mortality and tumor control after postoperative radiotherapy for non-small-cell lung cancer: calculations from clinical trials. Int J Radiat Oncol Biol Phys. 2007;68:1047–52.CrossRefPubMed Miles EF, Kelsey CR, Kirkpatrick JP, Marks LB. Estimating the magnitude and field-size dependence of radiotherapy-induced mortality and tumor control after postoperative radiotherapy for non-small-cell lung cancer: calculations from clinical trials. Int J Radiat Oncol Biol Phys. 2007;68:1047–52.CrossRefPubMed
15.
go back to reference Bogart JA, Aronowitz JN. Localized non-small cell lung cancer: adjuvant radiotherapy in the era of effective systematic therapy. Clin Cancer Res. 2005;11:5004S–10.CrossRefPubMed Bogart JA, Aronowitz JN. Localized non-small cell lung cancer: adjuvant radiotherapy in the era of effective systematic therapy. Clin Cancer Res. 2005;11:5004S–10.CrossRefPubMed
16.
17.
go back to reference Billiet C, Decaluwé H, Peeters S, Vansteenkiste J, Dooms C, Haustermans K, et al. Modern post-operative radiotherapy for stage III non-small cell lung cancer may improve local control and survival: a meta-analysis. Radiother Oncol. 2014;110:3–8.CrossRefPubMed Billiet C, Decaluwé H, Peeters S, Vansteenkiste J, Dooms C, Haustermans K, et al. Modern post-operative radiotherapy for stage III non-small cell lung cancer may improve local control and survival: a meta-analysis. Radiother Oncol. 2014;110:3–8.CrossRefPubMed
18.
go back to reference Feng W, Fu XL, Cai XW, Yang HJ, Wu KL, Fan M, et al. Patterns of local-Regional failure in completely resected stage IIIA(N2) non-small cell lung cancer cases: implications for postoperative radiation therapy clinical target volume design. Int J Radiat Oncol Biol Phys. 2014;88:1100–7.CrossRefPubMed Feng W, Fu XL, Cai XW, Yang HJ, Wu KL, Fan M, et al. Patterns of local-Regional failure in completely resected stage IIIA(N2) non-small cell lung cancer cases: implications for postoperative radiation therapy clinical target volume design. Int J Radiat Oncol Biol Phys. 2014;88:1100–7.CrossRefPubMed
19.
go back to reference National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: non-small-cell lung cancer, v.4.2014. Available at: www.nccn.org. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: non-small-cell lung cancer, v.4.2014. Available at: www.​nccn.​org.
20.
21.
go back to reference Trodella L, Granone P, Valente S, Valentini V, Balducci M, Mantini G, et al. Adjuvant radiotherapy in non-small cell lung cancer with pathological stage I: definitive results of a phase III randomized trial. Radiother Oncol. 2002;62:11–9.CrossRefPubMed Trodella L, Granone P, Valente S, Valentini V, Balducci M, Mantini G, et al. Adjuvant radiotherapy in non-small cell lung cancer with pathological stage I: definitive results of a phase III randomized trial. Radiother Oncol. 2002;62:11–9.CrossRefPubMed
22.
go back to reference Higgins KA, Chino JP, Berry M, Ready N, Boyd J, Yoo DS, et al. Local failure in resected N1 lung cancer: implications for adjuvant therapy. Int J Radiat Oncol Biol Phys. 2012;83:727–33.CrossRefPubMed Higgins KA, Chino JP, Berry M, Ready N, Boyd J, Yoo DS, et al. Local failure in resected N1 lung cancer: implications for adjuvant therapy. Int J Radiat Oncol Biol Phys. 2012;83:727–33.CrossRefPubMed
23.
go back to reference Rusch VW, Asamura H, Watanabe H, Giroux DJ, Rami-Porta R, Goldstraw P. The IASLC lung cancer staging project: a proposal for a new international lymph node map in the forthcoming seventh edition of the TNM classification for lung cancer. J Thorac Oncol. 2009;4:568–77.CrossRefPubMed Rusch VW, Asamura H, Watanabe H, Giroux DJ, Rami-Porta R, Goldstraw P. The IASLC lung cancer staging project: a proposal for a new international lymph node map in the forthcoming seventh edition of the TNM classification for lung cancer. J Thorac Oncol. 2009;4:568–77.CrossRefPubMed
24.
go back to reference Watkins C, Huang X, Latimer N, Tang Y, Wright EJ. Adjusting overall survival for treatment switches: commonly used methods and practical application. Pharm Stat. 2013;12:348–57.CrossRefPubMed Watkins C, Huang X, Latimer N, Tang Y, Wright EJ. Adjusting overall survival for treatment switches: commonly used methods and practical application. Pharm Stat. 2013;12:348–57.CrossRefPubMed
25.
go back to reference Bracarda S, Bellmunt J, Melichar B, Négrier S, Bajetta E, Ravaud A, et al. Overall survival in patients with metastatic renal cell carcinoma initially treated with bevacizumab plus interferon-α2a and subsequent therapy with tyrosine kinase inhibitors: a retrospective analysis of the phase III AVOREN trial. BJU Int. 2011;107:214–9.CrossRefPubMed Bracarda S, Bellmunt J, Melichar B, Négrier S, Bajetta E, Ravaud A, et al. Overall survival in patients with metastatic renal cell carcinoma initially treated with bevacizumab plus interferon-α2a and subsequent therapy with tyrosine kinase inhibitors: a retrospective analysis of the phase III AVOREN trial. BJU Int. 2011;107:214–9.CrossRefPubMed
26.
go back to reference Corso CD, Rutter CE, Wilson LD, Kim AW, Decker RH, Husain ZA. 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;10:148–55.CrossRefPubMed Corso CD, Rutter CE, Wilson LD, Kim AW, Decker RH, Husain ZA. 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;10:148–55.CrossRefPubMed
27.
go back to reference Robinson CG, Patel AP, Bradley JD, DeWees T, Waqar SN, Morgensztern D, 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 Clin Oncol. 2015;33:870–6.CrossRefPubMedPubMedCentral Robinson CG, Patel AP, Bradley JD, DeWees T, Waqar SN, Morgensztern D, 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 Clin Oncol. 2015;33:870–6.CrossRefPubMedPubMedCentral
28.
go back to reference Ichinose Y, Kato H, Koike T, Tsuchiya R, Fujisawa T, Shimizu N, et al. Overall survival and local recurrence of 406 completely resected stage IIIa-N2 non-small cell lung cancer patients: questionnaire survey of the Japan Clinical Oncology Group to plan for clinical trials. Lung Cancer. 2001;34:29–36.CrossRefPubMed Ichinose Y, Kato H, Koike T, Tsuchiya R, Fujisawa T, Shimizu N, et al. Overall survival and local recurrence of 406 completely resected stage IIIa-N2 non-small cell lung cancer patients: questionnaire survey of the Japan Clinical Oncology Group to plan for clinical trials. Lung Cancer. 2001;34:29–36.CrossRefPubMed
29.
go back to reference Sawyer TE, Bonner JA, Gould PM, Foote RL, Deschamps C, Trastek VF, et al. Effectiveness of postoperative irradiation in stage IIIA non-small cell lung cancer according to regression tree analyses of recurrence risks. Ann Thorac Surg. 1997;64:1402–7.CrossRefPubMed Sawyer TE, Bonner JA, Gould PM, Foote RL, Deschamps C, Trastek VF, et al. Effectiveness of postoperative irradiation in stage IIIA non-small cell lung cancer according to regression tree analyses of recurrence risks. Ann Thorac Surg. 1997;64:1402–7.CrossRefPubMed
30.
go back to reference Urban D, Bar J, Solomon B, Ball D. Lymph node ratio may predict the benefit of postoperative radiotherapy in non-small-cell lung cancer. J Thorac Oncol. 2013;8:940–6.CrossRefPubMed Urban D, Bar J, Solomon B, Ball D. Lymph node ratio may predict the benefit of postoperative radiotherapy in non-small-cell lung cancer. J Thorac Oncol. 2013;8:940–6.CrossRefPubMed
Metadata
Title
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
Authors
Wen Feng
Qin Zhang
Xiao-Long Fu
Xu-Wei Cai
Zheng-Fei Zhu
Huan-Jun Yang
Jia-Qing Xiang
Ya-Wei Zhang
Hai-Quan Chen
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1326-6

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