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Radiological changes following second-line zoledronic acid treatment in breast cancer patients with bone metastases

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Abstract

Initiation of bisphosphonate therapy in bisphosphonate-naïve patients is known to be associated with radiological changes such as increased bone density in both osteolytic and osteoblastic metastases. It is not known, however, whether switching from a second-generation bisphosphonate to a more potent agent is associated with similar changes. This study aimed to prospectively explore radiological changes, as assessed by thoracolumbar CT scanning, in patients switching from an early generation bisphosphonate (i.e., oral clodronate or intravenous pamidronate) to intravenous zoledronic acid. Patients with progressive bone metastases despite use of an earlier generation bisphosphonate were switched to zoledronic acid as part of a study to evaluate the palliative benefit of this intervention. Quantitative computed tomography (QCT) scanning of the thoracolumbar spine was carried out at baseline, and repeated 4 months after commencing zoledronic acid. The effect of this change of therapy was explored in terms of bone density, as well as volume of osteolytic and osteoblastic disease. Fifteen patients were assessed. Switching of bisphosphonate therapy was associated with a significant increase in bone density, and an increase in osteoblastic volume. There was an insignificant trend towards reduced osteolytic volume. In conclusion, switching from early generation bisphosphonates to a more potent agent is associated with radiological changes similar to those seen when commencing a bisphosphonate in treatment-naïve patients. This is consistent with the observed palliative benefit. The use of QCT may be of benefit in the monitoring of bone metastases.

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Abbreviations

CT:

Computed tomography

QCT:

Quantitative computed tomography

References

  1. Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics, 2002. CA: Cancer J Clin 55:74–108. doi:10.3322/canjclin.55.2.74

    Article  Google Scholar 

  2. Coleman RE (1997) Skeletal complications of malignancy. Cancer 80:1588–1594. doi:10.1002/(SICI)1097-0142(19971015)80:8+<1588::AID-CNCR9>3.0.CO;2-G

    Article  PubMed  CAS  Google Scholar 

  3. Lipton A, Theriault RL, Hortobagyi GN, Simeone J, Knight RD, Mellars K et al (2000) Pamidronate prevents skeletal complications and is effective palliative treatment in women with breast carcinoma and osteolytic bone metastases: long term follow-up of two randomized, placebo-controlled trials. Cancer 88:1082–1090. doi:10.1002/(SICI)1097-0142(20000301)88:5<1082::AID-CNCR20>3.0.CO;2-Z

    Article  PubMed  CAS  Google Scholar 

  4. Kohno N, Aogi K, Minami H, Nakamura S, Asaga T, Iino Y et al (2005) Zoledronic acid significantly reduces skeletal complications compared with placebo in Japanese women with bone metastases from breast cancer: a randomized, placebo-controlled trial. J Clin Oncol 23:3314–3321. doi:10.1200/JCO.2005.05.116

    Article  PubMed  CAS  Google Scholar 

  5. Hortobagyi GN, Theriault RL, Lipton A, Porter L, Blayney D, Sinoff C et al (1998) Long-term prevention of skeletal complications of metastatic breast cancer with pamidronate. Protocol 19 Aredia Breast Cancer Study Group. J Clin Oncol 16:2038–2044

    PubMed  CAS  Google Scholar 

  6. Theriault RL, Lipton A, Hortobagyi GN, Leff R, Glück S, Stewart JF et al (1999) Pamidronate reduces skeletal morbidity in women with advanced breast cancer and lytic bone lesions: a randomized, placebo-controlled trial. Protocol 18 Aredia Breast Cancer Study Group. J Clin Oncol 17:846–854

    PubMed  CAS  Google Scholar 

  7. Conte PF, Latreille J, Mauriac L, Calabresi F, Santos R, Campos D et al (1996) Delay in progression of bone metastases in breast cancer patients treated with intravenous pamidronate: results from a multinational randomized controlled trial. J Clin Oncol 14:2552–2559

    PubMed  CAS  Google Scholar 

  8. Hultborn R, Gundersen S, Ryden S, Holmberg E, Carstensen J, Wallgren UB et al (1999) Efficacy of pamidronate in breast cancer with bone metastases: a randomized, double-blind placebo-controlled multicenter study. Anticancer Res 19:3383–3392

    PubMed  CAS  Google Scholar 

  9. Clamp A, Danson S, Nguyen H, Cole D, Clemons M (2004) Assessment of therapeutic response in patients with metastatic bone disease. Lancet Oncol 5:607–616. doi:10.1016/S1470-2045(04)01596-7

    Article  PubMed  Google Scholar 

  10. Ciarelli MJ, Goldstein SA, Kuhn JL, Cody DD, Brown MB (1991) Evaluation of orthogonal mechanical properties and density of human trabecular bone from the major metaphyseal regions with materials testing and computed tomography. J Orthop Res 9:674–682. doi:10.1002/jor.1100090507

    Article  PubMed  CAS  Google Scholar 

  11. Keyak JH, Lee IY, Skinner HB (1994) Correlations between orthogonal mechanical properties and density of trabecular bone: use of different densitometric measures. J Biomed Mater Res 28:1329–1336. doi:10.1002/jbm.820281111

    Article  PubMed  CAS  Google Scholar 

  12. Kaneko TS, Bell JS, Pejcic MR, Tehranzadeh J, Keyak JH (2004) Mechanical properties, density and quantitative CT scan data of trabecular bone with and without metastases. J Biomech 37:523–530. doi:10.1016/j.jbiomech.2003.08.010

    Article  PubMed  Google Scholar 

  13. Coleman RE, Houston S, Purohit OP, Rubens RD, Kandra A, Ford J (1998) A randomised phase II study of oral pamidronate for the treatment of bone metastases from breast cancer. Eur J Cancer 34:820–824. doi:10.1016/S0959-8049(97)10155-1

    Article  PubMed  CAS  Google Scholar 

  14. Glover D, Lipton A, Keller A, Miller AA, Browning S, Fram RJ et al (1994) Intravenous pamidronate disodium treatment of bone metastases in patients with breast cancer. A dose-seeking study. Cancer 74:2949–2955. doi:10.1002/1097-0142(19941201)74:11<2949::AID-CNCR2820741110>3.0.CO;2-Q

    Article  PubMed  CAS  Google Scholar 

  15. Hortobagyi GN, Theriault RL, Porter L, Blayney D, Lipton A, Sinoff C et al (1996) Efficacy of pamidronate in reducing skeletal complications in patients with breast cancer and lytic bonemetastases. Protocol 19 Aredia Breast Cancer Study Group. N Engl J Med 335:1785–1791. doi:10.1056/NEJM199612123352401

    Article  PubMed  CAS  Google Scholar 

  16. Berenson JR, Lichtenstein A, Porter L, Dimopoulos MA, Bordoni R, George S et al (1996) Efficacy of pamidronate in reducing skeletal events in patients with advanced multiple myeloma. N Engl J Med 334:488–493. doi:10.1056/NEJM199602223340802

    Article  PubMed  CAS  Google Scholar 

  17. Kylmala T, Taube T, Tammela TLJ, Risteli L, Risteli J, Elomaa I (1997) Concomitant i.v. and oral clodronate in the relief of bone pain—a double blind placebo-controlled study in patients with prostate cancer. Br J Cancer 76:939–942

    PubMed  CAS  Google Scholar 

  18. Clemons MJ, Dranitsaris G, Ooi WS, Yogendran G, Sukovic T, Wong BY et al (2006) A phase II trial evaluating the palliative benefit of second-line zoledronic acid in breast cancer patients with either a skeletal related event or progressive bone metastases despite first line bisphosphonate therapy. J Clin Oncol 24:4895–4900. doi:10.1200/JCO.2006.05.9212

    Article  PubMed  CAS  Google Scholar 

  19. Hardisty M, Gordon L, Agarwal P, Skrinskas T, Whyne C (2007) Quantitative characterization of metastatic disease in the spine. Part I. Semiautomated segmentation using atlas-based deformable registration and the level set method. Med Phys 34:3127–3134. doi:10.1118/1.2746498

    Article  PubMed  CAS  Google Scholar 

  20. Whyne C, Hardisty M, Wu F, Skrinskas T, Clemons M, Gordon L, Basran PS (2007) Quantitative characterization of metastatic disease in the spine. Part II. Histogram-based analyses. Med Phys 34:3279–3285. doi:10.1118/1.2756939

    Article  PubMed  Google Scholar 

  21. Coleman RE, Rubens RD (1987) The clinical course of bone metastases from breast cancer. Br J Cancer 55:61–66

    PubMed  CAS  Google Scholar 

  22. Wong DA, Fornasier VL, MacNab I (1990) Spinal metastases: the obvious, the occult, and the impostors. Spine 15:1–4. doi:10.1097/00007632-199001000-00001

    Article  PubMed  CAS  Google Scholar 

  23. Arguello F, Baggs RB, Duerst RE, Johnstone L, McQueen K, Frantz CN (1990) Pathogenesis of vertebral metastasis and epidural spinal cord compression. Cancer 65:98–106. doi:10.1002/1097-0142(19900101)65:1<98::AID-CNCR2820650121>3.0.CO;2-K

    Article  PubMed  CAS  Google Scholar 

  24. Whyne C (1999) Development of guidelines for the prophylactic treatment of metastatically involved vertebral bodies. Ph.D. Thesis, U.C. Berkeley/U.C. San Francisco

  25. Quattrocchi CC, Santini D, Dell’aia P, Piciucchi S, Leoncini E, Vincenzi B et al (2007) A prospective analysis of CT density measurements of bone metastases after treatment with zoledronic acid. Skeletal Radiol 36:1121–1127. doi:10.1007/s00256-007-0388-1

    Article  PubMed  Google Scholar 

  26. Quattrocchi CC, Piciucchi S, Sammarra M, Santini D, Vincenzi B, Tonini G et al (2007) Bone metastases in breast cancer: higher prevalence of osteosclerotic lesions. Radiol Med 112:1049–1059. doi:10.1007/s11547-007-0205-x

    Article  PubMed  CAS  Google Scholar 

  27. Hunter AE, Green DJ, Hunter JB (1993) Osteoporosis as a late complication of allogeneic bone marrow transplantation. Paper presented at the Fourth International Symposium on Osteoporosis, Hong Kong, 27 March to 2 April 1993

  28. Reinbold WD, Wannenmacher M, Hodapp N, Adler CP (1989) Osteodensitometry of vertebral metastases after radiotherapy using quantitative computed tomography. Skeletal Radiol 18:517–521. doi:10.1007/BF00351751

    Article  PubMed  CAS  Google Scholar 

  29. Stutz JA, Barry BP, Maslanka W, Sokal M, Green DJ, Pearson D (1998) Bone density: is it affected by orchidectomy and radiotherapy given for stage I seminoma of the testis? Clin Oncol 10:44–49. doi:10.1016/S0936-6555(98)80113-1

    Article  CAS  Google Scholar 

  30. Chow E, Holden L, Rubenstein J, Christakis M, Sixel K, Vidmar M et al (2004) CT evaluation of breast cancer patients with osteolytic bone metastases undergoing palliative radiotherapy: a feasibility study. Radiother Oncol 70:291–294. doi:10.1016/j.radonc.2004.01.009

    Article  PubMed  Google Scholar 

  31. Anderson ND, Colyer RA, Riley LH (1979) Skeletal changes during prolonged external irradiation: alterations in marrow, growth plate and osteoclast populations. Johns Hopkins Med J 145:73–83

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was part funded by grants from the Canadian Breast Cancer Research Alliance, and the Canadian Breast Cancer Foundation-Ontario Chapter.

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Correspondence to M. Clemons.

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Amir, E., Whyne, C., Freedman, O.C. et al. Radiological changes following second-line zoledronic acid treatment in breast cancer patients with bone metastases. Clin Exp Metastasis 26, 479–484 (2009). https://doi.org/10.1007/s10585-009-9247-x

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  • DOI: https://doi.org/10.1007/s10585-009-9247-x

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