Top

Published in:

01-10-2009 | Musculoskeletal

Imaging response to systemic therapy for bone metastases

Authors: Tobias Bäuerle, Wolfhard Semmler

Published in: European Radiology | Issue 10/2009

Abstract

In patients with osteotropic primary tumours such as breast and prostate cancer, imaging treatment response of bone metastases is essential for the clinical management. After treatment of skeletal metastases, morphological changes, in particular of bone structure, occur relatively late and are difficult to quantify using conventional X-rays, CT or MRI. Early treatment response in these lesions can be assessed from functional imaging techniques such as dynamic contrast-enhanced techniques by MRI or CT and by diffusion-weighted MRI, which are quantifiable. Among the techniques within nuclear medicine, PET offers the acquisition of quantifiable parameters for response evaluation. PET, therefore, especially in combination with CT and MRI using hybrid techniques, holds great promise for early and quantifiable assessment of treatment response in bone metastases. This review summarises the classification systems and the use of imaging techniques for evaluation of treatment response and suggests parameters for the early detection and quantification of response to systemic therapy.

Galasko C (1981) The anatomy and pathways of skeletal metastases. GK Hall, Boston

Coleman RE (2006) Clinical features of metastatic bone disease and risk of skeletal morbidity. Clin Cancer Res 12:6243s–6249sPubMed

Fan K, Peng CF (1983) Predicting the probability of bone metastasis through histological grading of prostate carcinoma: a retrospective correlative analysis of 81 autopsy cases with antemortem transurethral resection specimen. J Urol 130:708–711PubMed

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

Mundy GR (2002) Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer 2:584–593PubMed

Mastro AM, Gay CV, Welch DR (2003) The skeleton as a unique environment for breast cancer cells. Clin Exp Metastasis 20:275–284PubMed

Body JJ (2005) Overview of osteoclast inhibitors. Wiley, Chichester

Luckman SP, Hughes DE, Coxon FP et al (1998) Nitrogen-containing bisphosphonates inhibit the mevalonate pathway and prevent post-translational prenylation of GTP-binding proteins, including Ras. J Bone Miner Res 13:581–589PubMed

Michaelson MD, Smith MR (2005) Bisphosphonates for treatment and prevention of bone metastases. J Clin Oncol 23:8219–8224

10.

Daubine F, Le Gall C, Gasser J et al (2007) Antitumor effects of clinical dosing regimens of bisphosphonates in experimental breast cancer bone metastasis. J Natl Cancer Inst 99:322–330PubMed

11.

Fournier PG, Daubine F, Lundy MW et al (2008) Lowering bone mineral affinity of bisphosphonates as a therapeutic strategy to optimize skeletal tumor growth inhibition in vivo. Cancer Res 68:8945–8953PubMed

12.

Slamon DJ, Leyland-Jones B, Shak S et al (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344:783–792PubMed

13.

Miller K, Wang M, Gralow J et al (2007) Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 357:2666–2676PubMed

14.

Aldridge SE, Lennard TW, Williams JR et al (2005) Vascular endothelial growth factor acts as an osteolytic factor in breast cancer metastases to bone. Br J Cancer 92:1531–1537PubMed

15.

Bäuerle T, Hilbig H, Bartling S et al (2008) Bevacizumab inhibits breast cancer induced osteolysis, surrounding soft tissue metastasis, and angiogenesis in rats as visualized by VCT and MRI. Neoplasia 10:511–520PubMed

16.

Bäuerle T, Bartling S, Berger M et al (2008) Imaging anti-angiogenic treatment response with DCE-VCT, DCE-MRI and DWI in an animal model of breast cancer bone metastasis. Eur J Radiol doi:10.1016/j.ejrad.2008.10.020 PubMed

17.

Burstein HJ, Elias AD, Rugo HS et al (2008) Phase II study of sunitinib malate, an oral multitargeted tyrosine kinase inhibitor, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol 26:1810–1816PubMed

18.

Dahut WL, Scripture C, Posadas E et al (2008) A phase II clinical trial of sorafenib in androgen-independent prostate cancer. Clin Cancer Res 4:209–214

19.

Murray LJ, Abrams TJ, Long KR et al (2003) SU11248 inhibits tumor growth and CSF-1R-dependent osteolysis in an experimental breast cancer bone metastasis model. Clin Exp Metastasis 20:757–766PubMed

20.

Hayward JL, Carbone PP, Heusen JC et al (1977) Assessment of response to therapy in advanced breast cancer. Br J Cancer 35:292–298PubMed

21.

Hayward JL, Carbone PP, Rubens RD et al (1978) Assessment of response to therapy in advanced breast cancer (an amendment). Br J Cancer 38:201PubMed

22.

World Health Organisation (1979) WHO handbook for reporting results of cancer treatment. WHO, Geneva

23.

Therasse P, Arbuck SG, Eisenhauer EA et al (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92:205–216PubMed

24.

Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247PubMed

25.

Hamaoka T, Madewell JE, Podoloff DA et al (2004) Bone imaging in metastatic breast cancer. J Clin Oncol 22:2942–2953PubMed

26.

Rybak LD, Rosenthal DI (2001) Radiological imaging for the diagnosis of bone metastases. Q J Nucl Med 45:53–64PubMed

27.

Coleman RE, Houston S, Purohit OP et al (1998) A randomised phase II study of oral pamidronate for the treatment of bone metastases from breast cancer. Eur J Cancer 34:820–824PubMed

28.

Krasnow AZ, Hellman RS, Timins ME et al (1997) Diagnostic bone scanning in oncology. Semin Nucl Med 27:107–141PubMed

29.

Woolfenden JM, Pitt MJ, Durie BG et al (1980) Comparison of bone scintigraphy and radiography in multiple myeloma. Radiology 134:723–728PubMed

30.

Hortobagyi GN, Libshitz HI, Seabold JE (1984) Osseous metastases of breast cancer. Clinical, biochemical, radiographic, and scintigraphic evaluation of response to therapy. Cancer 53:577–582PubMed

31.

Condon BR, Buchanan R, Garvie NW et al (1981) Assessment of progression of secondary bone lesions following cancer of the breast or prostate using serial radionuclide imaging. Br J Radiol 54:18–23PubMedCrossRef

32.

Vinholes J, Coleman R, Eastell R (1996) Effects of bone metastases on bone metabolism: implications for diagnosis, imaging and assessment of response to cancer treatment. Cancer Treat Rev 22:289–331PubMed

33.

Holder LE (1990) Clinical radionuclide bone imaging. Radiology 176:607–614PubMed

34.

Levenson RM, Sauerbrunn BJ, Bates HR et al (1983) Comparative value of bone scintigraphy and radiography in monitoring tumor response in systemically treated prostatic carcinoma. Radiology 146:513–518PubMed

35.

Janicek MJ, Hayes DF, Kaplan WD (1994) Healing flare in skeletal metastases from breast cancer. Radiology 192:201–204PubMed

36.

Coleman RE, Mashiter G, Whitaker KB et al (1988) Bone scan flare predicts successful systemic therapy for bone metastases. J Nucl Med 29:1354–1359PubMed

37.

Gillespie PJ, Alexander JL, Edelstyn GA (1975) Changes in 87mSr concentrations in skeletal metastases in patients responding to cyclical combination chemotherapy for advanced breast cancer. J Nucl Med 16:191–193PubMed

38.

Corcoran RJ, Thrall JH, Kyle RW et al (1976) Solitary abnormalities in bone scans of patients with extraosseous malignancies. Radiology 121:663–667PubMed

39.

O'Mara RE (1976) Skeletal scanning in neoplastic disease. Cancer 37:480–486PubMed

40.

Citrin DL (1977) Problems and limitations of bone scanning with the 99Tcm-phosphates. Clin Radiol 28:97–105PubMed

41.

Lecouvet FE, Malghem J, Michaux L et al (1999) Skeletal survey in advanced multiple myeloma: radiographic versus MR imaging survey. Br J Haematol 106:35–39PubMed

42.

Libshitz HI, Hortobagyi GN (1981) Radiographic evaluation of therapeutic response in bony metastases of breast cancer. Skeletal Radiol 7:159–165PubMed

43.

Coombes RC, Dady P, Parsons C et al (1983) Assessment of response of bone metastases to systemic treatment in patients with breast cancer. Cancer 52:610–614PubMed

44.

Hortobagyi GN, Theriault RL, Porter L et al (1996) Efficacy of pamidronate in reducing skeletal complications in patients with breast cancer and lytic bone metastases. Protocol 19 Aredia Breast Cancer Study Group. N Engl J Med 335:1785–1791PubMed

45.

Coleman RE, Woll PJ, Miles M (1988) Treatment of bone metastases from breast cancer with (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD). Br J Cancer 58:621–625PubMed

46.

Krahe T, Nicolas V, Ring S et al (1989) Diagnostic evaluation of full x-ray pictures and computed tomography of bone tumors of the spine. Rofo 150:13–19PubMed

47.

Kido DK, Gould R, Taati F (1978) Comparative sensitivity of CT scans, radiographs and radionuclide bone scans in detecting metastatic calvarial lesions. Radiology 128:371–375PubMed

48.

Sundaram M, McGuire MH (1988) Computed tomography or magnetic resonance for evaluating the solitary tumor or tumor-like lesion of bone? Skeletal Radiol 17:393–401PubMed

49.

Poitout D, Gaujoux G, Lempidakis M et al (1991) X-ray computed tomography or MRI in the assessment of bone tumor extension. Chirurgie 117:488–490PubMed

50.

Helms CA, Cann CE, Brunelle FO et al (1981) Detection of bone-marrow metastases using quantitative computed tomography. Radiology 140:745–750PubMed

51.

Mazess RB, Vetter J (1985) The influence of marrow on measurement of trabecular bone using computed tomography. Bone 6:349–351PubMed

52.

Bellamy EA, Nicholas D, Ward M et al (1987) Comparison of computed tomography and conventional radiology in the assessment of treatment response of lytic bony metastases in patients with carcinoma of the breast. Clin Radiol 38:351–355PubMed

53.

Krishnamurthy GT, Tubis M, Hiss J et al (1977) Distribution pattern of metastatic bone disease. A need for total body skeletal image. JAMA 237:2504–2506PubMed

54.

Horger M, Claussen CD, Bross-Bach U et al (2005) Whole-body low-dose multidetector row-CT in the diagnosis of multiple myeloma: an alternative to conventional radiography. Eur J Radiol 54:289–297PubMed

55.

Schmidt GP, Reiser MF, Baur-Melnyk A (2007) Whole-body imaging of the musculoskeletal system: the value of MR imaging. Skeletal Radiol 36:1109–1119PubMed

56.

Mulkens TH, Bellinck P, Baeyaert M et al (2005) Use of an automatic exposure control mechanism for dose optimization in multi-detector row CT examinations: clinical evaluation. Radiology 237:213–223PubMed

57.

Taoka T, Mayr NA, Lee HJ et al (2001) Factors influencing visualization of vertebral metastases on MR imaging versus bone scintigraphy. AJR Am J Roentgenol 176:1525–1530PubMed

58.

Lecouvet FE, Geukens D, Stainier A et al (2007) Magnetic resonance imaging of the axial skeleton for detecting bone metastases in patients with high-risk prostate cancer: diagnostic and cost-effectiveness and comparison with current detection strategies. J Clin Oncol 25:3281–3287PubMed

59.

Zimmer WD, Berquist TH, McLeod RA et al (1985) Bone tumors: magnetic resonance imaging versus computed tomography. Radiology 155:709–718PubMed

60.

Imamura F, Kuriyama K, Seto T et al (2000) Detection of bone marrow metastases of small cell lung cancer with magnetic resonance imaging: early diagnosis before destruction of osseous structure and implications for staging. Lung Cancer 27:189–197PubMed

61.

Petren-Mallmin M, Andreasson I, Nyman R et al (1993) Detection of breast cancer metastases in the cervical spine. Acta Radiol 34:543–548PubMed

62.

Sugimura K, Kajitani A, Okizuka H et al (1991) Assessing response to therapy of spinal metastases with gadolinium-enhanced MR imaging. J Magn Reson Imaging 1:481–484PubMed

63.

Saip P, Tenekeci N, Aydiner A et al (1999) Response evaluation of bone metastases in breast cancer: value of magnetic resonance imaging. Cancer Invest 17:575–580PubMed

64.

Brown AL, Middleton G, MacVicar AD et al (1998) T1-weighted magnetic resonance imaging in breast cancer vertebral metastases: changes on treatment and correlation with response to therapy. Clin Radiol 53:493–501PubMed

65.

Tombal B, Rezazadeh A, Therasse P et al (2005) Magnetic resonance imaging of the axial skeleton enables objective measurement of tumor response on prostate cancer bone metastases. Prostate 65:178–187PubMed

66.

Steinborn MM, Heuck AF, Tiling R et al (1999) Whole-body bone marrow MRI in patients with metastatic disease to the skeletal system. J Comput Assist Tomogr 23:123–129PubMed

67.

Baur-Melnyk A, Buhmann S, Becker C et al (2008) Whole-body MRI versus whole-body MDCT for staging of multiple myeloma. AJR Am J Roentgenol 190:1097–1104PubMed

68.

Patterson DM, Padhani AR, Collins DJ (2008) Technology insight: water diffusion MRI—a potential new biomarker of response to cancer therapy. Nat Clin Pract Oncol 5:220–233PubMed

69.

Dzik-Jurasz A, Domenig C, George M et al (2002) Diffusion MRI for prediction of response of rectal cancer to chemoradiation. Lancet 360:307–308PubMed

70.

Theilmann RJ, Borders R, Trouard TP et al (2004) Changes in water mobility measured by diffusion MRI predict response of metastatic breast cancer to chemotherapy. Neoplasia 6:831–837PubMed

71.

Galons JP, Altbach MI, Paine-Murrieta GD et al (1999) Early increases in breast tumor xenograft water mobility in response to paclitaxel therapy detected by non-invasive diffusion magnetic resonance imaging. Neoplasia 1:113–117PubMed

72.

Charles-Edwards EM, deSouza NM (2006) Diffusion-weighted magnetic resonance imaging and its application to cancer. Cancer Imaging 6:135–143PubMed

73.

Lee KC, Sud S, Meyer CR et al (2007) An imaging biomarker of early treatment response in prostate cancer that has metastasized to the bone. Cancer Res 67:3524–3528PubMed

74.

Lee KC, Bradley DA, Hussain M et al (2007) A feasibility study evaluating the functional diffusion map as a predictive imaging biomarker for detection of treatment response in a patient with metastatic prostate cancer to the bone. Neoplasia 9:1003–1011PubMed

75.

Collier BD Jr, Hellman RS, Krasnow AZ (1987) Bone SPECT. Semin Nucl Med 17:247–266PubMed

76.

Gates GF (1988) SPECT imaging of the lumbosacral spine and pelvis. Clin Nucl Med 13:907–914PubMed

77.

Podoloff DA, Kim EE, Haynie TP (1992) SPECT in the evaluation of cancer patients: not quo vadis; rather, ibi fere summus. Radiology 183:305–317PubMed

78.

Blau M, Ganatra R, Bender MA (1992) 18F-fluoride for bone imaging. Semin Nucl Med 2:31–37

79.

Hawkins RA, Choi Y, Huang SC et al (1992) Evaluation of the skeletal kinetics of fluorine-18-fluoride ion with PET. J Nucl Med 33:633–642PubMed

80.

Koukouraki S, Strauss LG, Georgoulias V et al (2006) Comparison of the pharmacokinetics of 68Ga-DOTATOC and [18F]FDG in patients with metastatic neuroendocrine tumours scheduled for 90Y-DOTATOC therapy. Eur J Nucl Med Mol Imaging 33:1115–1122PubMed

81.

Kumar P, Mercer J, Doerkson C et al (2007) Clinical production, stability studies and PET imaging with 16-alpha-[18F]fluoroestradiol ([18F]FES) in ER positive breast cancer patients. J Pharm Pharm Sci 10:256s–265sPubMed

82.

Cook GJ, Houston S, Rubens R et al (1998) Detection of bone metastases in breast cancer by 18FDG PET: differing metabolic activity in osteoblastic and osteolytic lesions. J Clin Oncol 16:3375–3379PubMed

83.

Shreve PD, Grossman HB, Gross MD et al (1996) Metastatic prostate cancer: initial findings of PET with 2-deoxy-2-[F-18]fluoro-D-glucose. Radiology 199:751–756PubMed

84.

Moon DH, Maddahi J, Silverman DH et al (1998) Accuracy of whole-body fluorine-18-FDG PET for the detection of recurrent or metastatic breast carcinoma. J Nucl Med 39:431–435PubMed

85.

Dehdashti F, Flanagan FL, Mortimer JE et al (1999) Positron emission tomographic assessment of “metabolic flare” to predict response of metastatic breast cancer to antiestrogen therapy. Eur J Nucl Med 26:51–56PubMed

86.

Mortimer JE, Dehdashti F, Siegel BA et al (2001) Metabolic flare: indicator of hormone responsiveness in advanced breast cancer. J Clin Oncol 19:2797–2803PubMed

87.

Sugawara Y, Fisher SJ, Zasadny KR et al (1998) Preclinical and clinical studies of bone marrow uptake of fluorine-1-fluorodeoxyglucose with or without granulocyte colony-stimulating factor during chemotherapy. J Clin Oncol 16:173–180PubMed

88.

Young H, Baum R, Cremerius U et al (1999) Measurement of clinical and subclinical tumour response using [18F]-fluorodeoxyglucose and positron emission tomography: review and 1999 EORTC recommendations. European Organization for Research and Treatment of Cancer (EORTC) PET Study Group. Eur J Cancer 35:1773–1782PubMed

89.

Groves AM, Beadsmoore CJ, Cheow HK et al (2006) Can 16-detector multislice CT exclude skeletal lesions during tumour staging? Implications for the cancer patient. Eur Radiol 16:1066–1073PubMed

90.

Utsunomiya D, Shiraishi S, Imuta M et al (2006) Added value of SPECT/CT fusion in assessing suspected bone metastasis: comparison with scintigraphy alone and nonfused scintigraphy and CT. Radiology 238:264–271PubMed

91.

Du Y, Cullum I, Illidge TM, Ell PJ (2007) Fusion of metabolic function and morphology: sequential [18F]fluorodeoxyglucose positron-emission tomography/computed tomography studies yield new insights into the natural history of bone metastases in breast cancer. J Clin Oncol 25:3440–3447PubMed

92.

Tateishi U, Gamez C, Dawood S et al (2008) Bone metastases in patients with metastatic breast cancer: morphologic and metabolic monitoring of response to systemic therapy with integrated PET/CT. Radiology 247:189–196PubMedCrossRef

93.

Miller JC, Pien HH, Sahani D et al (2005) Imaging angiogenesis: applications and potential for drug development. J Natl Cancer Inst 97:172–187PubMedCrossRef

94.

Rehman S, Jayson GC (2005) Molecular imaging of antiangiogenic agents. Oncologist 10:92–103PubMed

95.

Kiessling F, Jugold M, Woenne EC et al (2007) Non-invasive assessment of vessel morphology and function in tumors by magnetic resonance imaging. Eur Radiol 17:2136–2148PubMed

96.

Rosen MA, Schnall MD (2007) Dynamic contrast-enhanced magnetic resonance imaging for assessing tumor vascularity and vascular effects of targeted therapies in renal cell carcinoma. Clin Cancer Res 13:770s–776sPubMed

97.

Willett CG, Boucher Y, di Tomaso E et al (2004) Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Nat Med 10:145–147PubMed

98.

Brix G, Semmler W, Port R (1991) Pharmacokinetic parameters in CNS Gd-DTPA enhanced MR imaging. J Comput Assist Tomogr 15:621–628PubMed

99.

Dafni H, Kim SJ, Bankson JA (2008) Macromolecular dynamic contrast-enhanced (DCE)-MRI detects reduced vascular permeability in a prostate cancer bone metastasis model following anti-platelet-derived growth factor receptor (PDGFR) therapy, indicating a drop in vascular endothelial growth factor receptor (VEGFR) activation. Magn Reson Med 60:822–833PubMed

100.

Hillengass J, Wasser K, Delorme S et al (2007) Lumbar bone marrow microcirculation measurements from dynamic contrast-enhanced magnetic resonance imaging is a predictor of event-free survival in progressive multiple myeloma. Clin Cancer Res 13:475–481PubMed

101.

Nosas-Garcia S, Moehler T, Wasser K et al (2005) Dynamic contrast-enhanced MRI for assessing the disease activity of multiple myeloma: a comparative study with histology and clinical markers. J Magn Reson Imaging 22:154–162PubMed

102.

Wasser K, Moehler T, Nosas-Garcia S et al (2005) Correlation of MRI and histopathology of bone marrow in patients with multiple myeloma. Rofo 177:1116–1122PubMed

Title: Imaging response to systemic therapy for bone metastases
Authors: Tobias Bäuerle
Wolfhard Semmler
Publication date: 01-10-2009
Publisher: Springer-Verlag
Published in: European Radiology / Issue 10/2009
Print ISSN: 0938-7994
Electronic ISSN: 1432-1084
DOI: https://doi.org/10.1007/s00330-009-1443-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Imaging response to systemic therapy for bone metastases

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 10/2009

An unusual cause of an acute abdomen (2009: 10a)

Prospective ECG-triggered axial CT at 140-kV tube voltage improves coronary in-stent restenosis visibility at a lower radiation dose compared with conventional retrospective ECG-gated helical CT

Introduction of an individually optimized protocol for the injection of contrast medium for coronary CT angiography

Preoperative fMRI in tumour surgery

Diffusion-weighted MRI provides additional value to conventional dynamic contrast-enhanced MRI for detection of hepatocellular carcinoma

Value of multidetector CT in decision making regarding surgery in patients with small-bowel obstruction due to adhesion