Early osteosclerotic changes predict chemotherapy response in non-small-cell lung cancer patients with bone metastases

  • Dailin Rong
  • Yize Mao
  • Qiuxia Yang
  • Shuhang Xu
  • Qianqian Zhao
  • Rong Zhang
Computed Tomography
  • 18 Downloads

Abstract

Objectives

To explore the relationship between osteosclerotic changes and chemotherapy response in non-small-cell lung cancer (NSCLC) patients with bone metastases (BM).

Methods

Fifty-two NSCLC patients with BM were enrolled from 1 January 2010–31 June 2015 and divided into two groups based on their CT features: an osteosclerotic change (OC) group and a no-osteosclerotic change (NOC) group. The disease control rate (DCR) was evaluated, and progression-free survival (PFS) was analysed using Kaplan-Meier curves. Univariate and multivariate Cox regression analyses were performed to analyse the factors that could affect PFS.

Results

Osteosclerotic changes were observed in 35/52 patients. The median interval when osteosclerotic changes occurred was 2 months (range 1–3 months) after chemotherapy. The OC group had a significantly higher 3-month DCR than the NOC group (p < 0.001). The OC group had a higher 1-year PFS rate than the NOC group (1-year PFS: 74.9% vs. 30.2%, p < 0.001). Univariate Cox regression analysis indicated that pathological subtype (HR = 4.419; 95% CI = 1.635–11.941, p = 0.003) and osteosclerotic changes (HR = 0.199; 95% CI = 0.083–0.477, p < 0.001) were significant predictors of PFS.

Conclusion

Early osteosclerotic changes predict chemotherapy response in NSCLC patients with BM.

Key Points

Osteosclerotic changes were prevalent CT features after chemotherapy in NSCLC patients.

Osteosclerotic changes were positively related to increased 3-month DCR.

Osteosclerotic changes were positively related to increased 1-year PFS rate.

Keywords

Osteosclerotic changes Non-small-cell lung cancer Bone metastases Computed tomography Progression-free survival 

Abbreviations

BM

Bone metastases

CT

Computed tomography

DCR

Disease control rate

NOC

Without osteosclerotic changes

NSCLC

Non-small-cell lung cancer

OC

Osteosclerotic changes

PFS

Progression-free survival

Notes

Acknowledgements

We thank the native English-speaking scientists of American Journal Experts for editing our manuscript.

Compliance with ethical standards

Guarantor

The scientific guarantor of this publication is Rong Zhang, Sun Yat-Sen University Cancer Center

Conflict of interest

The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article.

Statistics and biometry

No complex statistical methods were necessary for this paper.

Informed consent

Written informed consent was not required for this study because this was a retrospective study

Ethical approval

Institutional Review Board approval was obtained.

Methodology

• retrospective

• observational

• performed at one institution

Supplementary material

330_2017_5253_MOESM1_ESM.docx (2.4 mb)
ESM 1 (DOCX 2481 kb)

References

  1. 1.
    Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127:2893–2917CrossRefPubMedGoogle Scholar
  2. 2.
    Yu JL, Simmons C, Victor JC et al (2011) Impact of new chemotherapeutic and targeted agents on survival in stage IV non-small cell lung cancer. Oncologist 16:1307–1315CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Ettinger DS, Akerley W, Borghaei H et al (2013) Non-small cell lung cancer, version 2.2013. J Natl Compr Cancer Netw 11:645–653 quiz 653CrossRefGoogle Scholar
  4. 4.
    Torre LA, Siegel RL, Jemal A (2016) Lung Cancer Statistics. Adv Exp Med Biol 893:1–19CrossRefPubMedGoogle Scholar
  5. 5.
    Reck M, Popat S, Reinmuth N et al (2014) Metastatic non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 25:iii27–iii39CrossRefPubMedGoogle Scholar
  6. 6.
    Besse B, Adjei A, Baas P et al (2014) 2nd ESMO Consensus Conference on Lung Cancer: non-small-cell lung cancer first-line/second and further lines of treatment in advanced disease. Ann Oncol 25:1475–1484CrossRefPubMedGoogle Scholar
  7. 7.
    Ettinger DS, Wood DE, Akerley W et al (2016) NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 4.2016. J Natl Compr Canc Netw 14:255–264CrossRefPubMedGoogle Scholar
  8. 8.
    Hoang T, Dahlberg SE, Sandler AB, Brahmer JR, Schiller JH, Johnson DH (2012) Prognostic models to predict survival in non-small-cell lung cancer patients treated with first-line paclitaxel and carboplatin with or without bevacizumab. J Thorac Oncol Off Publ Int Assoc Study Lung Cancer 7:1361–1368Google Scholar
  9. 9.
    Kouloulias EV, Kouvaris RJ, Antypas C et al (2003) An intra-patient dose-escalation study of disodium pamidronate plus radiotherapy versus radiotherapy alone for the treatment of osteolytic metastases. Monitoring of recalcification using image-processing techniques. Strahlenther Onkol 179:471–479CrossRefPubMedGoogle Scholar
  10. 10.
    Quattrocchi CC, Piciucchi S, Sammarra M et al (2007) Bone metastases in breast cancer: higher prevalence of osteosclerotic lesions. Radiol Med 112:1049CrossRefPubMedGoogle Scholar
  11. 11.
    Amir E, Whyne C, Freedman OC et al (2009) Radiological changes following second-line zoledronic acid treatment in breast cancer patients with bone metastases. Clin Exp Metastasis 26:479–484CrossRefPubMedGoogle Scholar
  12. 12.
    Yamashita Y, Aoki T, Hanagiri T et al (2012) Osteosclerotic lesions in patients treated with gefitinib for lung adenocarcinomas: a sign of favorable therapeutic response. Skeletal Radiol 41:409–414CrossRefPubMedGoogle Scholar
  13. 13.
    Rief H, Bischof M, Bruckner T et al (2013) The stability of osseous metastases of the spine in lung cancer – a retrospective analysis of 338 cases. Radiat Oncol 8:1–7CrossRefGoogle Scholar
  14. 14.
    Robert F, Christian E, Thomas B et al (2015) Bone density as a marker for local response to radiotherapy of spinal bone metastases in women with breast cancer: a retrospective analysis. Radiat Oncol 10:1–7CrossRefGoogle Scholar
  15. 15.
    Huang Q, Ouyang X (2013) Bone markers for monitoring efficacy in patients with bone metastases receiving zoledronic acid: a review of published data. Int J Biol Markers 28:242–248CrossRefPubMedGoogle Scholar
  16. 16.
    Hamaoka T, Madewell JE, Podoloff DA, Hortobagyi GN, Ueno NT (2004) Bone imaging in metastatic breast cancer. J Clin Oncol Off J Am Soc Clin Oncol 22:2942–2953CrossRefGoogle Scholar
  17. 17.
    Watanabe H, Okada M, Kaji Y et al (2009) New response evaluation criteria in solid tumours-revised RECIST guideline (version 1.1). Gan To Kagaku Ryoho 36:2495–2501PubMedGoogle Scholar
  18. 18.
    Weilbaecher KN, Guise TA, Mccauley LK (2011) Cancer to bone: a fatal attraction. Nat Rev Cancer 11:411–425CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Ell B, Kang Y (2012) SnapShot: Bone Metastasis. Cell 151:690CrossRefPubMedGoogle Scholar
  20. 20.
    Pienta KJ, Robertson BA, Coffey DS, Taichman RS (2013) The Cancer Diaspora: Metastasis beyond the seed and soil hypothesis. Clin Cancer Res An Off J Am Assoc Cancer Res 19:5849–5855CrossRefGoogle Scholar
  21. 21.
    Roato I (2014) Bone metastases: When and how lung cancer interacts with bone. World J Clin Oncol 5:149–155CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Suva LJ, Washam C, Nicholas RW, Griffin RJ (2011) Bone metastasis: mechanisms and therapeutic opportunities. Nat Rev Endocrinol 7:208–218CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Coleman RE (1997) Skeletal complications of malignancy. Cancer 80:1588–1594CrossRefPubMedGoogle Scholar
  24. 24.
    Weidle UH, Birzele F, Kollmorgen G, Rüger R (2016) Molecular Mechanisms of Bone Metastasis. Cancer Genomics Proteomics 13:1CrossRefPubMedGoogle Scholar
  25. 25.
    Zheng H, Li W, Kang Y (2017) Tumor-Stroma Interactions in Bone Metastasis: Molecular Mechanisms and Therapeutic Implications. Cold Spring Harb Symp Quant Biol 81:151–161Google Scholar
  26. 26.
    Chang CY, Simeone FJ, Torriani M, Bredella MA (2017) Quantitative contrast-enhanced CT attenuation evaluation of osseous metastases following chemotherapy. Skeletal Radiol.  https://doi.org/10.1007/s00256-017-2706-6
  27. 27.
    Hayashi N, Costelloe CM, Hamaoka T et al (2013) A prospective study of bone tumor response assessment in metastatic breast cancer. Clin Breast Cancer 13:24–30CrossRefPubMedGoogle Scholar

Copyright information

© European Society of Radiology 2017

Authors and Affiliations

  1. 1.State Key Laboratory of Oncology in Southern ChinaGuangzhouPeople’s Republic of China
  2. 2.Department of RadiologySun Yat-Sen University Cancer CenterGuangzhouPeople’s Republic of China
  3. 3.Department of UltrasoundThe Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhouPeople’s Republic of China

Personalised recommendations