Skip to main content
Log in

Stereotactic body radiotherapy versus conventional radiotherapy for early-stage small cell lung cancer

  • Original Research
  • Published:
Journal of Radiation Oncology

Abstract

Purpose

This study was designed to compare survival outcomes for non-surgically managed T1-T2N0M0 small cell lung cancer (SCLC) patients who received either stereotactic body radiation therapy (SBRT) or conventionally fractionated radiotherapy (CFRT) using the National Cancer Database (NCDB).

Methods

The NCDB was queried between 2004 and 2015 for patients with T1-T2N0M0 SCLC. Patients must have been treated with curative intent SBRT or CFRT (delivered daily or twice daily, 45–70 Gy) with or without chemotherapy. The primary outcome was overall survival (OS). A subset analysis of patients receiving chemotherapy was also performed. A propensity score matching (PSM) analysis was performed to compare OS among patients who received chemotherapy.

Results

We evaluated 1378 patients in the general cohort. Multivariable Cox regression analysis (MVA) in the general cohort revealed that SBRT was significantly associated with improved survival (HR 0.68, p < 0.001) along with receipt of chemotherapy (HR 0.63, p < 0.001). SBRT patients were less likely to receive chemotherapy compared with CFRT patients (p < 0.01). In the chemotherapy subset of 1096 patients, on MVA, there was a trend in favor of the SBRT group (HR 0.73, p = 0.06). A 3:1 PSM analysis on the chemotherapy subset found similar results on MVA with a trend in favor of SBRT (p = 0.06).

Conclusion

Patients with T1-2N0M0 SCLC treated with SBRT regimens incorporating chemotherapy had comparable outcomes with those treated with concurrent chemoradiotherapy using standard fractionation. Treatment paradigms for T1-2N0M0 SCLC incorporating SBRT warrant further exploration and should incorporate chemotherapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Govindan R, Page N, Morgensztern D, Read W, Tierney R, Vlahiotis A, Spitznagel EL, Piccirillo J (2006) Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: analysis of the surveillance, epidemiologic, and end results database. J Clin Oncol 24(28):4539–4544. https://doi.org/10.1200/JCO.2005.04.4859

    Article  Google Scholar 

  2. Siegel RL, Miller KD, Jemal A (2018) Cancer statistics, 2018. CA Cancer J Clin 68(1):7–30. https://doi.org/10.3322/caac.21442

    Article  Google Scholar 

  3. Demedts IK, Vermaelen KY, Van Meerbeeck JP (2010) Treatment of extensive-stage small cell lung carcinoma: current status and future prospects. Eur Respir J 35(1):202–215. https://doi.org/10.1183/09031936.00105009

    Article  CAS  PubMed  Google Scholar 

  4. Turrisi AT, Kim K, Blum R, Sause WT, Livingston RB, Komaki R, Wagner H, Aisner S, Johnson DH (1999) Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med 340:265–271. https://doi.org/10.1056/NEJM199901283400403

    Article  CAS  PubMed  Google Scholar 

  5. Yu JB, Decker RH, Detterbeck FC, Wilson LD (2010) Surveillance epidemiology and end results evaluation of the role of surgery for stage I small cell lung cancer. J Thorac Oncol 5:215–219. https://doi.org/10.1097/JTO.0b013e3181cd3208

    Article  PubMed  Google Scholar 

  6. Church TR, Black WC, Aberle DR et al (2013) Results of initial low-dose computed tomographic screening for lung cancer. N Engl J Med 368:1980–1991. https://doi.org/10.1056/NEJMoa1209120

    Article  CAS  PubMed  Google Scholar 

  7. Aberle DR, Adams AM, Berg CD et al (2011) Reduced lung cancer mortality with low-dose computed tomographic screening. N Engl J Med 365:395–409. https://doi.org/10.1056/NEJMoa1102873

    Article  PubMed  Google Scholar 

  8. Oudkerk M, Devaraj A, Vliegenthart R, Henzler T, Prosch H, Heussel CP, Bastarrika G, Sverzellati N, Mascalchi M, Delorme S, Baldwin DR, Callister ME, Becker N, Heuvelmans MA, Rzyman W, Infante MV, Pastorino U, Pedersen JH, Paci E, Duffy SW, de Koning H, Field JK (2017) European position statement on lung cancer screening. Lancet Oncol 18(12):e754–e766. https://doi.org/10.1016/S1470-2045(17)30861-6

    Article  PubMed  Google Scholar 

  9. Knight SB, Crosbie PA, Balata H, Chudziak J, Hussell T, Dive C (2017) Progress and prospects of early detection in lung cancer. Open Biol 7(9):170070. https://doi.org/10.1098/rsob.170070

    Article  CAS  Google Scholar 

  10. Almquist D, Mosalpuria K, Ganti AK (2016) Multimodality therapy for limited-stage small-cell lung cancer. J Oncol Pract 12(2):111–117. https://doi.org/10.1200/JOP.2015.009068

    Article  PubMed  Google Scholar 

  11. Yang C-FJ, Chan DY, Speicher PJ, Gulack BC, Wang X, Hartwig MG, Onaitis MW, Tong BC, D’Amico TA, Berry MF, Harpole DH (2016) Role of adjuvant therapy in a population-based cohort of patients with early-stage small-cell lung cancer. J Clin Oncol 34(10):1057–1064. https://doi.org/10.1200/JCO.2015.63.8171

    Article  PubMed  PubMed Central  Google Scholar 

  12. Shioyama Y, Nakamura K, Sasaki T, Ohga S, Yoshitake T, Nonoshita T, Asai K, Terashima K, Matsumoto K, Hirata H, Honda H (2013) Clinical results of stereotactic body radiotherapy for stage I small-cell lung cancer: a single institutional experience. J Radiat Res 54(1):108–112. https://doi.org/10.1093/jrr/rrs075

    Article  PubMed  Google Scholar 

  13. Ly NB, Allen PK, Lin SH (2014) Stereotactic body radiation therapy for stage I small cell lung cancer: a single institutional case series and review of the literature. J Radiat Oncol 3(3):285–291

    Article  Google Scholar 

  14. Videtic GMM, Stephans KL, Woody NM, Pennell NA, Shapiro M, Reddy CA, Djemil T (2013) Stereotactic body radiation therapy-based treatment model for stage I medically inoperable small cell lung cancer. Pract Radiat Oncol 3(4):301–306. https://doi.org/10.1016/j.prro.2012.10.003

    Article  PubMed  Google Scholar 

  15. Timmerman R, Paulus R, Galvin J, Michalski J, Straube W, Bradley J, Fakiris A, Bezjak A, Videtic G, Johnstone D, Fowler J, Gore E, Choy H (2010) Stereotactic body radiation therapy for inoperable early stage lung cancer. JAMA. 303(11):1070–1076. https://doi.org/10.1001/jama.2010.261

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Stahl JM, Corso CD, Verma V, Park HS, Nath SK, Husain ZA, Simone CB II, Kim AW, Decker RH (2017) Trends in stereotactic body radiation therapy for stage I small cell lung cancer. Lung Cancer 103:11–16. https://doi.org/10.1016/j.lungcan.2016.11.009

    Article  PubMed  Google Scholar 

  17. National Comprehensive Cancer Network (2019) Small cell cancer (version 2.2019). Retrieved from https://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf. Accessed 20 Dec 2018

  18. Bilimoria KY, Stewart AK, Winchester DP, Ko CY (2008) The National Cancer Data Base: a powerful initiative to improve cancer care in the United States. Ann Surg Oncol 15(3):683–690. https://doi.org/10.1245/s10434-007-9747-3

    Article  PubMed  PubMed Central  Google Scholar 

  19. National Cancer Database. Data dictionary participant user files. http://ncdbpuf.facs.org/node/259?q=print-pdf-all. Published 2016. Accessed 1 Nov 2017

  20. Austin PC (2009) The relative ability of different propensity score methods to balance measured covariates between treated and untreated subjects in observational studies. Med Decis Mak 29(6):661–677. https://doi.org/10.1177/0272989X09341755

    Article  Google Scholar 

  21. Nyman J, Hallqvist A, Lund JÅ, Brustugun OT, Bergman B, Bergström P, Friesland S, Lewensohn R, Holmberg E, Lax I (2016) SPACE – a randomized study of SBRT vs conventional fractionated radiotherapy in medically inoperable stage I NSCLC. Radiother Oncol 121(1):1–8. https://doi.org/10.1016/j.radonc.2016.08.015

    Article  PubMed  Google Scholar 

  22. Verma V, Simone C, Allen PLS (2017) Outcomes of stereotactic body radiotherapy for T1-2 N0 small cell carcinoma based on addition of chemotherapy and prophylactic cranial irradiation: a multicenter analysis. Clin Lung Cancer. 18(6):675–681.e1. https://doi.org/10.1016/j.cllc.2017.03.009

    Article  PubMed  PubMed Central  Google Scholar 

  23. Ahmed Z, Grover P, Kennedy KF, Masood A, Davis JR, Subramanian J (2017) Predictors for chemotherapy in early stage small cell lung carcinoma (SCLC): a National Cancer Database (NCDB) analysis. Lung Cancer 113:85–87. https://doi.org/10.1016/j.lungcan.2017.09.004

    Article  PubMed  Google Scholar 

  24. Shioyama Y, Onishi H, Takayama K, Matsuo Y, Takeda A, Yamashita H, Miyakawa A, Murakami N, Aoki M, Matsushita H, Matsumoto Y, Shibamoto Y, Japanese Radiological Society Multi-Institutional SBRT Study Group (JRS-SBRTSG) (2018) Clinical outcomes of stereotactic body radiotherapy for patients with stage I small-cell lung cancer: analysis of a subset of the Japanese Radiological Society Multi-Institutional SBRT Study Group Database. Technol Cancer Res Treat 17:1533033818783904. https://doi.org/10.1177/1533033818783904

    Article  PubMed  PubMed Central  Google Scholar 

  25. Onishi H, Shirato H, Nagata Y et al (2007) Hypofractionated stereotactic radiotherapy (HypoFXSRT) for stage I non-small cell lung cancer: updated results of 257 patients in a Japanese multi-institutional study. J Thorac Oncol 2(7 Suppl 3):S94–S100. https://doi.org/10.1097/JTO.0b013e318074de34

    Article  Google Scholar 

  26. Jeppesen SS, Schytte T, Jensen HR, Brink C, Hansen O (2013) Stereotactic body radiation therapy versus conventional radiation therapy in patients with early stage non-small cell lung cancer: an updated retrospective study on local failure and survival rates. Acta Oncol (Madr) 52(7):1552–1558. https://doi.org/10.3109/0284186X.2013.813635

    Article  Google Scholar 

  27. Ball D, Mai T, Vinod S, Babington S, Ruben J, Kron T, Chesson B, Herschtal A, Rezo A, Elder C, Skala M, Wirth A, Wheeler G, Lim A, Vanevski M, Shaw M (2017) MA 13.07 a randomized trial of SABR vs conventional radiotherapy for inoperable stage I non-small cell lung cancer: TROG09.02 (CHISEL). J Thorac Oncol 12(11):S1853. https://doi.org/10.1016/j.jtho.2017.09.565

    Article  Google Scholar 

  28. Winther-Larsen A, Hoffmann L, Moeller DS, Khalil AA, Knap MM (2015) Evaluation of factors associated with loco-regional failure and survival in limited disease small cell lung cancer patients treated with chemoradiotherapy. Acta Oncol (Madr). 54(9):1574–1581. https://doi.org/10.3109/0284186X.2015.1062135

    Article  CAS  Google Scholar 

  29. van Meerbeeck JP, Fennell DA, De Ruysscher DKM et al (2011) Small-cell lung cancer. Lancet. 378(9804):1741–1755. https://doi.org/10.1016/S0140-6736(11)60165-7

    Article  PubMed  Google Scholar 

  30. Sarvi S, Mackinnon AC, Avlonitis N, Bradley M, Rintoul RC, Rassl DM, Wang W, Forbes SJ, Gregory CD, Sethi T (2014) CD133+ cancer stem-like cells in small cell lung cancer are highly tumorigenic and chemoresistant but sensitive to a novel neuropeptide antagonist. Cancer Res 74(5):1554–1565. https://doi.org/10.1158/0008-5472.CAN-13-1541

    Article  CAS  PubMed  Google Scholar 

  31. Servat J, Verlicchi A, Rosell R (2016) Cancer stem cells in small cell lung cancer. Transl Lung Cancer Res 5(1):16–25. https://doi.org/10.3978/j.issn.2218-6751.2016.01.01

    Article  CAS  Google Scholar 

  32. Bao S, Wu Q, McLendon RE et al (2006) Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 444(7120):756–760. https://doi.org/10.1038/nature05236

    Article  CAS  PubMed  Google Scholar 

  33. Phillips TM, McBride WH, Pajonk F (2006) The response of CD24-/low/CD44+ breast cancer-initiating cells to radiation. J Natl Cancer Inst 98(24):1777–1785. https://doi.org/10.1093/jnci/djj495

    Article  Google Scholar 

  34. Moding EJ, Mowery YM, Kirsch DG (2016) Opportunities for radiosensitization in the stereotactic body radiation therapy (SBRT) era. Cancer J (United States) 22(4):267–273. https://doi.org/10.1097/PPO.0000000000000203

    Article  CAS  Google Scholar 

  35. Brooks ED, Schoenhals JE, Tang C, Micevic G, Gomez DR, Chang JY, Welsh JW (2016) Stereotactic ablative radiation therapy combined with immunotherapy for solid tumors. Cancer J (United States). 22(4):257–266. https://doi.org/10.1097/PPO.0000000000000210

    Article  CAS  Google Scholar 

  36. Lee Y, Auh SL, Wang Y, Burnette B, Wang Y, Meng Y, Beckett M, Sharma R, Chin R, Tu T, Weichselbaum RR, Fu YX (2009) Therapeutic effects of ablative radiation on local tumor require CD8+T cells: changing strategies for cancer treatment. Blood. 114(3):589–595. https://doi.org/10.1182/blood-2009-02-206870

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Singh S, Parulekar W, Murray N, Feld R, Evans WK, Tu D, Shepherd FA (2005) Influence of sex on toxicity and treatment outcome in small-cell lung cancer. J Clin Oncol 23(4):850–856. https://doi.org/10.1200/JCO.2005.03.171

    Article  PubMed  Google Scholar 

  38. Wheatley-Price P, Ma C, Ashcroft LF, Nankivell M, Stephens RJ, White SC, Lorigan P, Thatcher N, Blackhall FH, Shepherd FA (2010) The strength of female sex as a prognostic factor in small-cell lung cancer: a pooled analysis of chemotherapy trials from the Manchester Lung Group and Medical Research Council Clinical Trials Unit. Ann Oncol 21(2):232–237. https://doi.org/10.1093/annonc/mdp300

    Article  CAS  PubMed  Google Scholar 

  39. Paximadis P, Beebe-Dimmer JL, George J, Schwartz AG, Wozniak A, Gadgeel S (2018) Comparing treatment strategies for stage I small-cell lung cancer. Clin Lung Cancer 19(5):e559–e565. https://doi.org/10.1016/j.cllc.2018.03.017

    Article  PubMed  PubMed Central  Google Scholar 

  40. Auperin A, Arriagada R, Pignon J et al (1999) Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. Prophylatic Cranial Irradiation Overview Collaborative Group. N Engl J Med 341(7):476–484. https://doi.org/10.1056/NEJM199908123410703

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors also wish to acknowledge the Vanderbilt Institute for Clinical and Translational Research for their funding support.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Neil B. Newman.

Ethics declarations

Funding

This study was funded by the National Center for Advancing Translational Sciences (CTSA award no. UL1 TR002243) and the Vanderbilt Institute for Clinical and Translational Research.

Conflict of interest

Neil B. Newman received a grant in order to support biostatistical analysis. All other authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

Statement of informed consent was not applicable since the manuscript does not contain any patient data.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Newman, N.B., Sherry, A.D., Byrne, D.W. et al. Stereotactic body radiotherapy versus conventional radiotherapy for early-stage small cell lung cancer. J Radiat Oncol 8, 239–248 (2019). https://doi.org/10.1007/s13566-019-00395-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13566-019-00395-x

Keywords

Navigation