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Annals of Surgical Oncology

, Volume 25, Issue 5, pp 1245–1253 | Cite as

Concurrent Versus Sequential Chemoradiation Therapy in Completely Resected Pathologic N2 Non-Small Cell Lung Cancer: Propensity-Matched Analysis of the National Cancer Data Base

  • Amy C. Moreno
  • Waqar Haque
  • Vivek Verma
  • Penny Fang
  • Steven H. Lin
Thoracic Oncology

Abstract

Background

Following complete resection of pN2 non-small cell lung cancer (NSCLC), national guidelines recommend either sequential (sCRT) or concurrent chemoradiotherapy (cCRT). This is the largest study to date evaluating survival between both approaches. In sCRT patients, sequencing ‘chemotherapy first’ versus ‘radiotherapy first’ was also addressed.

Methods

The National Cancer Data Base (NCDB) was queried for patients with primary NSCLC undergoing surgery (without neoadjuvant radiotherapy or chemotherapy), pN2 disease with negative surgical margins, and receiving postoperative CRT. Multivariable logistic regression ascertained factors associated with cCRT administration. Kaplan–Meier analysis evaluated overall survival (OS), and Cox proportional hazards modeling determined variables associated with OS. Propensity matching was performed to address group imbalances and indication biases.

Results

Of 1924 total patients, 1115 (58%) received sCRT and 809 (42%) underwent cCRT. Median OS in the sCRT and cCRT cohorts was 53 months versus 37 months (p < 0.001); differences persisted following propensity matching (p = 0.002). In the sCRT population, there was a trend for higher OS in the ‘chemotherapy first’ group, relative to ‘radiotherapy first’ (55 vs. 44 months, p = 0.079), but there were no statistically apparent differences following propensity matching (p = 0.302).

Conclusions

For completely resected pN2 NSCLC, delivering adjuvant sCRT was associated with improved survival over cCRT. Toxicity-related factors may help to explain these results but need to be better addressed in further investigations. Differential sequencing of sCRT did not appear to affect survival.

Notes

Acknowledgments

Disclosure

Steven H. Lin has received research funding from Elekta, STCube Pharmaceuticals, Peregrine, Bayer, and Roche/Genentech, and has served as a consultant for AstraZeneca and received honorarium from US Oncology and ProCure. Amy C. Moreno, Waqar Haque, Vivek Verma, and Penny Fang declare no conflicts of interest.

Funding

No research support was received for this study.

Disclaimers

None. This work has not been previously presented or published in any form.

Supplementary material

10434_2018_6399_MOESM1_ESM.docx (18 kb)
Supplementary material 1 (DOCX 20 kb)
10434_2018_6399_MOESM2_ESM.tiff (51 kb)
Supplemental Figure 1. Effect of clinical nodal status (cN0-1 versus cN2) on overall survival in both the sCRT (A) and cCRT (B) patients. Supplementary material 2 (TIFF 52 kb)

References

  1. 1.
    National Comprehensive Cancer Network. Non-Small Cell Lung Cancer. Version 8.2017. https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf Accessed 21 Sep 2017.
  2. 2.
    Burdett S et al (2005) PORT Meta-analysis Trialists Group. Postoperative radiotherapy for non-small cell lung cancer. Cochrane Database Syst Rev. (18):CD002142.Google Scholar
  3. 3.
    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. Int J Radiat Oncol Biol Phys. 2008;72:695-701.CrossRefPubMedGoogle Scholar
  4. 4.
    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 Clin Oncol. 2006;24:2998–3006.CrossRefPubMedGoogle Scholar
  5. 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 Clin Oncol. 2015;33:870–876.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Curran WJ, Paulus R, Langer CJ et al. (2011) Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst. 103:1452–1460.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Auperin A, Le Pechoux C, Rolland E, et al. Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer. J Clin Oncol. 2010;28:2181–2190.CrossRefPubMedGoogle Scholar
  8. 8.
    Bradley JD, Paulus R, Graham MV, et al. Phase II trial of postoperative adjuvant paclitaxel/carboplatin and thoracic radiotherapy in resected stage II and IIIA non-small-cell lung cancer: promising long-term results of the Radiation Therapy Oncology Group–RTOG 9705. J Clin Oncol. 2005;23:3480–3487.CrossRefPubMedGoogle Scholar
  9. 9.
    Feigenberg SJ, Hanlon AL, Langer C, et al. A phase II study of concurrent carboplatin and paclitaxel and thoracic radiotherapy for completely resected stage II and IIIA non-small cell lung cancer. J Thorac Oncol. 2007;2:287–292.CrossRefPubMedGoogle Scholar
  10. 10.
    Kepka L, Socha J, Rucinska M, Wasilewska-Tesluk E, Komosinska K. Sequencing postoperative radiotherapy and adjuvant chemotherapy in non-small cell lung cancer: unanswered questions on the not evidence-based approach. J Thorac Dis. 2016;8:1381–1385.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Lee HW, Noh OK, Oh YT, et al. Radiation Therapy–First Strategy After Surgery With or Without Adjuvant Chemotherapy in Stage IIIA-N2 Non-Small Cell Lung Cancer. Int J Radiat Oncol Biol Phys. 2016;94:621–627.CrossRefPubMedGoogle Scholar
  12. 12.
    Bilimoria KY, Stewart AK, Winchester DP, et al. The National Cancer Data Base: A Powerful Initiative to Improve Cancer Care in the United States. Ann Surg Oncol. 2008;15:683–690.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Wang EH, Corso CD, Rutter CE, et al. Postoperative Radiation Therapy Is Associated With Improved Overall Survival in Incompletely Resected Stage II and III Non–Small-Cell Lung Cancer. J Clin Oncol. 2015;33:2727–2734.CrossRefPubMedGoogle Scholar
  14. 14.
    Amini A, Jones BL, McDermott JD, et al. Survival outcomes with concurrent chemoradiation for elderly patients with locally advanced head and neck cancer according to the National Cancer Data Base. Cancer. 2016;122:1533–1543.CrossRefPubMedGoogle Scholar
  15. 15.
    Haque W, Verma V, Butler EB, Teh BS. Definitive chemoradiation at high volume facilities is associated with improved survival in glioblastoma. J Neurooncol. 2017;135(1):173–181.CrossRefPubMedGoogle Scholar
  16. 16.
    Austin PC. Statistical criteria for selecting the optimal number of untreated subjects matched to each treated subject when using many-to- one matching on the propensity score. Am J Epidemiol. 2010; 172:1092–1097.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Rosenbaum PR, Rubin DB. The central role of the propensity score in observational studies for causal effects. Biometrika. 1983;70:15.CrossRefGoogle Scholar
  18. 18.
    Austin PC, Gootendorst P, Anderson GM. A comparison of the ability of different propensity score models to balance measured variables between treated and untreated subjects: a Monte Carlo study. Stat Med. 2007;26:734–753.CrossRefPubMedGoogle Scholar
  19. 19.
    Austin PC. Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples. Stat Med 2009;28:3083–3107.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    El-Sherif A, Fernando HC, Santos R, et al. Margin and local recurrence after sublobar resection of non-small cell lung cancer. Ann Surg Oncol. 2007;14:2400-2405.CrossRefPubMedGoogle Scholar
  21. 21.
    Gomez DR, Komaki R. Postoperative Radiation Therapy for Non-Small Cell Lung Cancer and Thymic Malignancies. Cancers. 2012;4:307–322.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Kim HI, Noh OK, Oh YT, et al. Comparison of concurrent chemoradiotherapy versus sequential radiochemotherapy in patients with completely resected non-small cell lung cancer. Radiat Oncol J. 2016;34:202–208.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    ClinicalTrials.gov. NCT00410683. Radiation therapy in treating patients with non-small cell lung cancer that has been completely removed by surgery (LUNG ART). Available at: https://clinicaltrials.gov/ct2/show/NCT00410683. Accessed 22 Sep 2017.

Copyright information

© Society of Surgical Oncology 2018

Authors and Affiliations

  • Amy C. Moreno
    • 1
  • Waqar Haque
    • 2
  • Vivek Verma
    • 3
  • Penny Fang
    • 1
  • Steven H. Lin
    • 1
  1. 1.Department of Radiation OncologyUniversity of Texas MD Anderson Cancer CenterHoustonUSA
  2. 2.Department of Radiation OncologyHouston Methodist HospitalHoustonUSA
  3. 3.Department of Radiation OncologyUniversity of Nebraska Medical CenterOmahaUSA

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