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Mortality after radiotherapy or surgery in the treatment of early stage non-small-cell lung cancer: a population-based study on recent developments

  • C. Ostheimer
  • C. Evers
  • F. Palm
  • R. Mikolajczyk
  • D. Vordermark
  • Daniel MedenwaldEmail author
Original Article – Clinical Oncology

Abstract

Background

Stereotactic body radiotherapy (SBRT) can achieve high tumour control with limited toxicity for inoperable early stage non-small-cell lung cancer (NSCLC) patients.

Patients and methods

The German Epidemiologic Cancer Registries from the Robert-Koch Institute were assessed. Periods according to the availability of SBRT were: (1) 2000–2003 (pre-SBRT); (2) 2004–2007 (interim); and (3) 2007–2014 (broad availability of SBRT). To assess the association of cancer-related parameters with mortality, hazard ratios (HR) from Cox proportional hazards models were computed. To evaluate the change of treatment-related mortality, we performed interaction analyses and the relative excess risk due to interaction (RERI, additive scale) was computed.

Results

A total of 16,292 patients with UICC stage I NSCLC diagnosed between 2000 and 2014 were analysed. Radiotherapy utilization increased from 5% in pre-SBRT era to 8.8% after 2007. In univariate analyses, survival in the whole cohort improved only marginally when 2000–2003 is compared to 2004–2007 (HR 0.92, 95% CI 0.85–1.01) or 2008–2014 (HR 0.93, 95% CI 0.86–1.01). Comparing surgery/radiotherapy, mortality in the radiotherapy group started from a 3.5-fold risk in 2000–2003 to 2.6 after 2007. The interaction analysis revealed a stronger improvement for radiotherapy (multiplicative scale for 2000–2003 vs. > 2007: 0.74, 95% CI 0.58–0.94). On an additive scale, treatment × period interaction revealed an RERI for 2000–2003 vs. > 2007 of − 1.18 (95% CI − 1.8, − 0.55).

Conclusions

Using population-based data, we observed a survival improvement in stage I lung cancer over time. With an increasing utilization of radiotherapy, a stronger improvement occurred in patients treated with radiotherapy when compared to surgery.

Keywords

Stereotactic body radiotherapy Lung cancer Stage I Non-small-cell lung cancer Radiotherapy Patterns of care Population-based analysis 

Abbreviations

UICC

Unité international contre le cancer

NSCLC

Non-small-cell lung cancer

VATS

Video-assisted thoracoscopic surgery

SBRT

Stereotactic body radiotherapy

OS

Overall survival

RT

Radiotherapy

RKI

Robert-Koch Institute

HR

Hazard ratio

Ci

Confidence interval

SCLC

Small-cell lung cancer

ECOG

Eastern Co-operative Oncology Group

Notes

Acknowledgements

We would like to thank the Robert Koch Institute (RKI), especially Dr. Klaus Kraywinkel, and the Epidemiologic Cancer Register in Germany for kindly providing the raw data for analysis.

Funding

No grant number is applicable.

Compliance with ethical standards

Conflict of interest

The authors have declared no conflicts of interest.

Supplementary material

432_2019_3013_MOESM1_ESM.tif (365 kb)
Figure S1: Flow chart of the cohort and the final number of patients taken into account. (TIFF 364 kb)
432_2019_3013_MOESM2_ESM.doc (23 kb)
Supplementary material 2 (DOC 23 kb)
432_2019_3013_MOESM3_ESM.doc (34 kb)
Table S1: Detailed survival characteristics (characteristics by treatment and period). (DOC 34 kb)
432_2019_3013_MOESM4_ESM.docx (14 kb)
Table S2: Results of the treatment-specific multivariate analyses of overall mortality. Effect estimates refer to hazard ratios with 95% confidence intervals from Cox-regression models. HR = hazard ratio, CI = 95% confidence interval (DOCX 13 kb)
432_2019_3013_MOESM5_ESM.doc (45 kb)
Table S3: Multivariate Interaction analyses comparing surgery and radiotherapy in relation to overall mortality considering only registries with higher data quality (Hager et al. 2015). Effect estimates refer to hazard ratios with 95% confidence intervals from Cox-regression models. Interaction analyses were performed on a multiplicative and additive scale. HR = hazard ratio, CI = 95% confidence interval, RERI = risk excess due to interaction (DOC 45 kb)
432_2019_3013_MOESM6_ESM.doc (45 kb)
Table S4: Multivariate Interaction analyses comparing surgery and radiotherapy in relation to overall mortality considering only cases with an age of 75 years or older. Effect estimates refer to hazard ratios with 95% confidence intervals from Cox-regression models. Interaction analyses were performed on a multiplicative and additive scale. HR = hazard ratio, CI = 95% confidence interval, RERI = risk excess due to interaction (DOC 45 kb)

References

  1. Cykert S, Dilworth-Anderson P, Monroe MH et al (2010) Factors associated with decisions to undergo surgery among patients with newly diagnosed early-stage lung cancer. JAMA 303:2368–2376CrossRefGoogle Scholar
  2. Eberle A, Jansen L, Castro F et al (2015) Lung cancer survival in Germany: a population-based analysis of 132,612 lung cancer patients. Lung Cancer 90:528–533CrossRefGoogle Scholar
  3. Goldstraw P, Crowley J, Chansky K et al (2007) The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM classification of malignant tumours. J Thorac Oncol 2:706–714CrossRefGoogle Scholar
  4. Guckenberger M, Allgaeuer M, Appold S et al (2013) Safety and efficacy of stereotactic body radiotherapy for stage 1 non-small-cell lung cancer in routine clinical practice: a patterns-of-care and outcome analysis. J Thorac Oncol 8:1050–1058CrossRefGoogle Scholar
  5. Guckenberger M, Andratschke Alheit H et al (2014) Definition of stereotactic body radiotherapy. Strahlenther Onkol 190:26–33CrossRefGoogle Scholar
  6. Haasbeek CJA, Palma D, Visser O et al (2012) Early-stage lung cancer in elderly patients: a population-based study of changes in treatment patterns and survival in the Netherlands. Ann Oncol 23:2743–2747CrossRefGoogle Scholar
  7. Hager B, Kraywinkel K, Keck B, Katalinic A, Meyer M, Zeissig SR, Stabenow R, Froehner M, Huber J (2015) Integrated prostate cancer centers might cause an overutilization of radiotherapy for low-risk prostate cancer: a comparison of treatment trends in the United States and Germany from 2004 to 2011. Radiother Oncol 115:90–95CrossRefGoogle Scholar
  8. Knol MJ, VanderWeele TJ, Groenwold RH, Klungel OH, Rovers MM, Grobbee DE (2011) Estimating measures of interaction on an additive scale for preventive exposures. Eur J Epidemiol 26:433–438CrossRefGoogle Scholar
  9. McCarthy M, Datta P, Khachatryan A et al (2008) Would compliance with cancer care standards improve survival for breast, colorectal and lung cancers? J Epidemiol Community Health 62:650–654CrossRefGoogle Scholar
  10. Morgensztern D, Goodgame B, Baggstrom MQ, Gao F, Govindan R (2008) The effect of FDG-PET on the stage distribution of non-small cell lung cancer. J Thorac Oncol 3(2):135–139CrossRefGoogle Scholar
  11. Palma D, Visser O, Lagerwaard FJ et al (2010) Impact of introducing stereotactic lung radiotherapy for elderly patients with stage I non–small-cell lung cancer: a population-based time-trend analysis. J Clin Oncol 35:5153–5159CrossRefGoogle Scholar
  12. Rami-Porta R, Crowley JJ, Goldstraw P (2009) The revised TNM staging system for lung cancer. Ann Thorac Cardiovasc Surg 15:4–9Google Scholar
  13. Shirvani SM, Chang JY, Roth JA (2013) Can stereotactic ablative radiotherapy in early stage lung cancers produce comparable success as surgery? Thorac Surg Clin 23:369–381CrossRefGoogle Scholar
  14. Siegel RL, Miller KD, Jemal A (2016) Cancer statistics. CA Cancer J Clin 66:7–30CrossRefGoogle Scholar
  15. Stegmaier C, Hentschel S, Hofstädter F, Katalinic A, Tillack A, Klinkhammer-Schalke M (2018) Das Manual der Krebsregistrierung, 2nd edn. W.-Zuckschwerdt-Verlag, MunichGoogle Scholar
  16. van der Drift MA, Karim-Kos HE, Siesling S, Groen HJM, Wouters MWJM, Coebergh J-W, de Vries E, Heijnen MLG (2012) Progress in standard of care therapy and modest survival benefits in the treatment of non-small cell lung cancer patients in the Netherlands in the last 20 years. J Thorac Oncol 7(2):291–298CrossRefGoogle Scholar
  17. Vest MT, Herrin J, Soulos PR et al (2013) Use of new treatment modalities for non-small cell lung cancer care in the Medicare population. Chest 143:429–435CrossRefGoogle Scholar
  18. Vittinghoff EC, McCulloch EC (2007) Relaxing the rule of ten events per variable in logistic and Cox regression. Am J Epidemiol 165:710–718CrossRefGoogle Scholar
  19. Wisnivesky JP, Bonomi M, Henschke C et al (2005) Radiation therapy for the treatment of unresected stage I–II non-small cell lung cancer. Chest 128:1461–1467CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Radiation OncologyMartin Luther UniversityHalleGermany
  2. 2.Institute of Medical Epidemiology, Biometry and InformaticsMartin Luther University Halle-WittenbergHalle (Saale)Germany

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