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Clinical and Translational Oncology
Published in: Clinical and Translational Oncology 12/2016

Open Access 01-12-2016 | Clinical Guides in Oncology

SEOM Clinical Guideline for bone metastases from solid tumours (2016)

Authors: C. Grávalos, C. Rodríguez, A. Sabino, M. Á. Seguí, J. A. Virizuela, A. Carmona, J. Cassinello, D. Isla, C. Jara, M. Martín

Published in: Clinical and Translational Oncology | Issue 12/2016

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Abstract

Bone metastases are common in many advanced solid tumours, being breast, prostate, thyroid, lung, and renal cancer the most prevalent. Bone metastases can produce skeletal-related events (SREs), defined as pathological fracture, spinal cord compression, need of bone irradiation or need of bone surgery, and hypercalcaemia. Patients with bone metastases experience pain, functional impairment and have a negative impact on their quality of life. Several imaging techniques are available for diagnosis of this disease. Bone-targeted therapies include zoledronic acid, a potent biphosfonate, and denosumab, an anti-RANKL monoclonal antibody. Both reduce the risk and/or delay the development of SREs in several types of tumours. Radium 233, an alpha-particle emitter, increases overall survival in patients with bone metastases from resistant castration prostate cancer. Multidisciplinary approach is essential and bone surgery and radiotherapy should be integrated in the treatment of bone metastases when necessary. This SEOM Guideline reviews bone metastases pathogenesis, clinical presentations, lab tests, imaging techniques for diagnosis and response assessment, bone-targeted agents, and local therapies, as radiation and surgery, and establishes recommendations for the management of patients with metastases to bone.
Literature
1.
Body JJ, Bartl R, Burchardt P, Delmas PD, Diel IJ, Fleisch H, et al. Current use of bisphosphonates in oncology. J Clin Oncol. 1998;16:3890–9.PubMed
2.
Fidler IJ. The pathogenesis of cancer metastases: the “seed and soil” hypothesis revisited. Nat Rev Cancer. 2003;3:453–8.CrossRefPubMed
3.
Coleman RE. Metastatic bone disease: clinical features, pathophysiology and treatment strategies. Cancer Treat Rev. 2015;27:165–76.CrossRef
4.
Healey JH, Turnbull AD, Miedema B, Lane JM. Acrometastases. A study of twenty-nine patients with osseous involvement of the hands and feet. J Bone Joint Surg Am. 1986;68:743–6.CrossRefPubMed
5.
Durán I, Garzón C, Sánchez A, García-Carbonero I, Pérez-Gracia JL, Seguí-Palmer MA, et al. Cost analysis of skeletal-related events in Spanish patients with bone metastases from solid tumours. Clin Transl Oncol. 2014;16:322–9.CrossRefPubMed
6.
Rodman GD. Mechanisms of bone metastasis. N Engl J Med. 2004;350:1655–64.CrossRef
7.
Yong M, Jensen AÖ, Jacobsen JB, Nørgaard M, Fryzek JP, Sørensen HT. Survival in breast cancer patients with bone metastases and skeletal-related events: a population-based cohort study in Denmark (1999–2007). Breast Cancer Res Treat. 2011;129:495–503.CrossRefPubMed
8.
Tanko LB, Karsdal MA, Christiansen C, Leeming DJ. Biochemical approach to the detection and monitoring of metastatic bone disease: what do we know and what questions need answers? Cancer Metastasis Rev. 2006;25:659–68.CrossRefPubMed
9.
Demers LM, Costa L, Lipton A. Biochemical markers and skeletal metastases. Cancer. 2000;88:2919–26.CrossRefPubMed
10.
Coleman RE, Major P, Lipton A, Brown JE, Lee KA, Smith M, et al. Predictive value of bone resorption and formation markers in cancer patients with bone metastases receiving the bisphosphonate and zoledronic acid. J Clin Oncol. 2005;23:4925–35.CrossRefPubMed
11.
Clemens M, Cole D, Gainford M. Can bone markers guide more effective treatment of bone metastases from breast cancer? Breast Cancer Res Treat. 2006;97:81–90.CrossRef
12.
Petrioli R, Rossi S, Caniggia M, Pozzessere D, Messinese S, Sabatino M, et al. Analysis of biochemical bone markers as prognostic factors for survival in patients with hormone-resistant prostate cancer and bone metastases. Urology. 2004;63:321–6.CrossRefPubMed
13.
Croset M, Santini D, Iuliani M, Fioramonti M, Zoccoli A, Vincenzi B, et al. MicroRNAs and bone metastasis: a new challenge. Molecules. 2014;19:10115–28.CrossRefPubMed
14.
Valencia K, Martín-Fernández M, Zandueta C, Ormazábal C, Martínez-Canarias S, Bandrés E, et al. miR-326 associates with biochemical markers of bone turnover in lung cancer bone metastasis. Bone. 2013;52:532–9.CrossRefPubMed
15.
Blake GM, Park-Holohan S-J, Cook GJR, Fogelman I. Quantitative studies of bone with the use of 18 F-fluoride and 99 m Tc-methylene diphosphonate. In: Seminars in nuclear medicine. Elsevier; 2001. p. 28–49.
16.
Katayama T, Kubota K, Machida Y, Toriihara A, Shibuya H. Evaluation of sequential FDG-PET/CT for monitoring bone metastasis of breast cancer during therapy: correlation between morphological and metabolic changes with tumour markers. Ann Nucl Med. 2012;26(5):426–35.CrossRefPubMed
17.
Utsunomiya D, Shiraishi S, Imuta M, Tomiguchi S, Kawanaka K, Morishita S, et al. Added value of SPECT/CT fusion in assessing suspected bone metastasis: comparison with scintigraphy alone and nonfused scintigraphy and CT. Radiology. 2006;238(1):264–71.CrossRefPubMed
18.
Palmedo H, Marx C, Ebert A, Kreft B, Ko Y, Türler A, et al. Whole-body SPECT/CT for bone scintigraphy: diagnostic value and effect on patient management in oncological patients. Eur J Nuclear Med Mol Imaging. 2014;41:59–67.CrossRef
19.
Rong J, Wang S, Ding Q, Yun M, Zheng Z, Ye S. Comparison of 18FDG PET-CT and bone scintigraphy for detection of bone metastases in breast cancer patients. A meta-analysis. Surg Oncol. 2013;22(2):86–91.CrossRefPubMed
20.
Abe K, Sasaki M, Kuwabara Y, Koga H, Baba S, Hayashi K, et al. Comparison of 18FDG-PET with 99mTc-HMDP scntigraphy for the detection of bone metastases in patients with breast cancer. Ann Nucl Med. 2005;19(7):573–9.CrossRefPubMed
21.
Reischauer C, Froehlich JM, Koh D-M, Graf N, Padevit C, John H, et al. Bone metastases from prostate cancer: assessing treatment response by using diffusion-weighted imaging and functional diffusion maps–initial observations. Radiology. 2010;257(2):523–31.CrossRefPubMed
22.
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228–47.CrossRefPubMed
23.
Cook GJ, Azad GK, Goh V. Imaging bone metastases in breast cancer: staging and response assessment. J Nucl Med. 2016;57(Suppl 1):27S–33S.CrossRefPubMed
24.
Coombes RC, Dady P, Parsons C, McCready VR, Ford HT, Gazet JC, et al. Assessment of response of bone metastases to systemic treatment in patients with breast cancer. Cancer. 1983;52(4):610–4.CrossRefPubMed
25.
Israel O, Goldberg A, Nachtigal A, Militianu D, Bar-Shalom R, Keidar Z, et al. FDG-PET and CT patterns of bone metastases and their relationship to previously administered anti-cancer therapy. Eur J Nucl Med Mole Imaging. 2006;33(11):1280–4.CrossRef
26.
Wahl RL, Jacene H, Kasamon Y, Lodge MA. From RECIST to PERCIST: evolving considerations for PET response criteria in solid tumours. J Nucl Med. 2009;50(Suppl 1):122S–50S.CrossRefPubMedPubMedCentral
27.
Brown AL, Middleton G, MacVicar AD, Husband JES. T1-weighted magnetic resonance imaging in breast cancer vertebral metastases: changes on treatment and correlation with response to therapy. Clin Radiol. 1998;53(7):493–501.CrossRefPubMed
28.
Decroisette C, Monnet I, Berard H, Quere G, Le Caer H, Bota S, et al. Epidemiology and treatment costs of bone metastases from lung cancer: a French prospective, observational, multicenter study (GFPC 0601). J Thorac Oncol. 2011;6:576–82.CrossRefPubMed
29.
30.
Coleman R, Body JJ, Aapro M, Hadji P, Herrstedt J; ESMO Guidelines Working Group. Bone health in cancer patients: ESMO Clinical Practice Guidelines. Ann Oncol. 2014;(Suppl 3); 25:iii124–iii137.
31.
Rosen SL, Gordon D, Dugan W Jr, Major P, Eisenberg PD, Provencher L, et al. Zoledronic acid is superior to pamidronate for the treatment of bone metastases in breast carcinoma patients with at least one osteolytic lesion. Cancer. 2004;100:36–43.CrossRefPubMed
32.
Kohno N, Aogi K, Minami H, Nakamura S, Asaga T, Iino Y, et al. 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. 2005;23:3314–21.CrossRefPubMed
33.
Hortobayi GN, Lipton A, Chew HC, Gradishar WJ, Sauter N, Mohanlal R, et al. Efficacy and safety of continued zoledronic acid every 4 weeks versus every 12 weeks in women with bone metastases from breast cancer: results of the OPTIMIZE-2 trial. J Clin Oncol. 2014;32:5s (suppl; abstr LBA9500).CrossRef
34.
Himelstein AL, Qin R, Novotny PJ, Seisler DK, Khatcheressian JL, Roberts JD, et al. CALGB 70604 (Alliance): A randomized phase III study of standard dosing vs. longer interval dosing of zoledronic acid in metastatic cancer. J Clin Oncol. 2015;33 (suppl; abstr 9501).
35.
Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004;351(15):1502–12.CrossRefPubMed
36.
37.
Saad F, Gleason DM, Murray R, Tchekmedyian S, Venner P, Lacombe L, et al. Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer. J Natl Cancer Inst. 2004;96(11):879–82.CrossRefPubMed
38.
Smith MR, Halabi S, Ryan CJ, Hussain A, Vogelzang N, Stadler W, et al. Randomized controlled trial of early zoledronic acid in men with castration-sensitive prostate cancer and bone metastases: results of CALGB 90202 (alliance). J Clin Oncol. 2014;32(11):1143–50.CrossRefPubMedPubMedCentral
39.
Rosen LS, Gordon D, Tchekmedian LS, Yanagihara R, Hirsh V, Krzakowski M, et al. Long-term efficacy and safety of zoledronic acid in the treatment of skeletal metastases in patients with non small cell lung cancer and other solid tumours: a randomized, phase III trial, double-blind, placebo-controlled trial. Cancer. 2004;100(12):2613–21.CrossRefPubMed
40.
Stopeck AT, Lipton A, Body JJ, Steger GG, Tonkin K, de Boer RH, et al. Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: a randomized, double-blind study. J Clin Oncol. 2010;28(35):5132–9.CrossRefPubMed
41.
Henry DH, Costa L, Goldwasser F, Hirsh V, Hungria V, Prausova J, et al. Randomized, double-blind study of denosumab versus zoledronic acid in the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma. J Clin Oncol. 2011;29(9):1125–32.CrossRefPubMed
42.
Stopeck AT, Lipton A, Body JJ, Steger GG, Tonkin K, de Boer RH, et al. Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: a randomized, double-blind study. J Clin Oncol. 2010;28(35):5132–9.CrossRefPubMed
43.
Fizazi K, Carducci M, Smith M, Damião R, Brown J, Karsh L, et al. Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet. 2011;377:813–22.CrossRefPubMedPubMedCentral
44.
Cassinello J, González del Alba A, Rivera F, Holgado E. SEOM guidelines for the treatment of bone metastases from solid tumours. Clin Transl Oncol. 2012;14:505–11.CrossRef
45.
Scagliotti GV, Hirsh V, Siena S, Henry DH, Woll PJ, Manegold C, et al. Overall survival improvement in patients with lung cancer and bone metastases treated with denosumab versus zoledronic acid: subgroup analysis from a randomized phase 3 study. J Thorac Oncol. 2012;7(12):1823–9.CrossRefPubMed
46.
Mundy GR. Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer. 2002;2(8):584–93.CrossRefPubMed
47.
Henry D, Vadjan-Raj S, Hirsh V, von Moos R, Hungria V, Costa L, et al. Delaying skeletal-related events in a randomized phase 3 study of denosumab versus zoledronic acid in patients with advanced cancer: an analysis of data of patients with solid tumours. Support Care Cancer. 2014;22(3):679–87.CrossRefPubMed
48.
Goyal J, Antonarakis ES. Bone-targeting radiopharmaceuticals for the treatment of prostate cancer with bone metastases. Cancer Lett. 2012;323(2):135–46.CrossRefPubMedPubMedCentral
49.
Lewington VJ, McEwan AJ, Ackery DM, Bayly RJ, Keeling DH, Macleod PM, et al. A prospective, randomised double-blind crossover study to examine the efficacy of strontium-89 in pain palliation in patients with advanced prostate cancer metastatic to bone. Eur J Cancer. 1991;27(8):954–8.CrossRefPubMed
50.
Sartor O, Reid RH, Hoskin PJ, Quick DP, Ell PJ, Coleman RE, et al. Samarium-153-lexidronam complex for treatment of painful bone metastases in hormone-refractory prostate cancer. Urology. 2004;63(5):940–5.CrossRefPubMed
51.
Nilsson S, Larsen RH, Fossa SD, Balteskard L, Borch KW, Westlin JE, et al. First clinical experience with alpha-emitting radium-223 in the treatment of skeletal metastases. Clin Cancer Res. 2005;11(12):4451–9.CrossRefPubMed
52.
Parker C, Nilsson S, Heinrich D, Helle SI, O’Sullivan JM, Fosså SD, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369(3):213–23.CrossRefPubMed
53.
Sartor O, Coleman R, Nilsson S, Heinrich D, Helle SI, O’Sullivan JM, et al. Effect of radium-223 dichloride on symptomatic skeletal events in patients with castration-resistant prostate cancer and bone metastases: results from a phase 3, double-blind, randomised trial. Lancet Oncol. 2014;15(7):738–46.CrossRefPubMed
54.
Hird A, Chow E, Zhang L, Wong R, Wu J, Sinclair E, et al. Determining the incidence of pain flare following palliative radiotherapy for symptomatic bone metastases: results from three Canadian cancer centers. Int J Radiat Oncol Biol Phys. 2009;75(1):193–7.CrossRefPubMed
55.
Fairchild A, Barnes E, Ghosh S, Ben-Josef E, Roos D, Hartsell W, et al. International patterns of practice in palliative radiotherapy for painful bone metastases: evidence-based practice? Int J Radiat Oncol Biol Phys. 2009;75(5):1501–10.CrossRefPubMed
56.
Hayashi S, Hoshi H, Iida T. Reirradiation with local field radiotherapy for painful bone metastases. Radiat Med. 2002;20(5):231–6.PubMed
57.
van der Linden Y, Lok J, Steenland E, Martijn H, van Houwelingen H, Marijnen CA, et al. Single fraction radiotherapy is efficacious: a further analysis of the Dutch Bone Metastasis Study controlling for the influence of retreatment. Int J Radiat Oncol Biol Phys. 2004;59(2):528–37.CrossRefPubMed
58.
Hoskin P, Price P, Eason D, Regan J, Austin D, Palmer S, et al. A prospective randomized trial of 4 Gy or 8 Gy single doses in the treatment of metastatic bone pain. Radiother Oncol. 1992;23:74–8.CrossRefPubMed
59.
Jhaveri P, Teh BS, Bloch C, Amato R, Butler EB, Paulino AC. Stereotactic body radiotherapy in the management of painful bone metastases. Oncology. 2008;22(7):782–8.PubMed
60.
Garg AK, Wang XS, Shiu AS, Allen P, Yang J, McAleer MF, et al. Prospective evaluation of spinal reirradiation by using stereotactic body radiation therapy: the University of Texas MD Anderson Cancer Center experience. Cancer. 2011;117(15):3509–16.CrossRefPubMed
61.
Sahgal A, Ames C, Chou D, Ma L, Huang K, Xu W, et al. Stereotactic body radiotherapy is effective salvage therapy for patients with prior radiation of spinal metastases. Int J Radiat Oncol Biol Phys. 2011;74(3):723–31.CrossRef
62.
Lutz S, Berk L, Chang E, Chow E, Hahn C, Hoskin P, et al. Palliative radiotherapy for bone metastases: an ASTRO evidence-based guideline. Int J Radiat Oncol Biol Phys. 2011;79:965–76.CrossRefPubMed
63.
Patchell RA, Tibbs PA, Regine WF, Payne R, Saris S, Kryscio RJ, et al. Direct decompressive surgical resection in the treatment of spinal cord compression caused by metastatic cancer: a randomised trial. Lancet. 2005;366:643–8.CrossRefPubMed
64.
65.
Powles T, Paterson A, McCloskey E, Schein P, Scheffler B, Tidy A, et al. Reduction in bone relapse and improved survival with oral clodronate for adjuvant treatment of operable breast cancer [ISRCTN83688026]. Breast Cancer Res. 2006;8:R13.CrossRefPubMedPubMedCentral
66.
Saarto T, Blomqvist C, Virkkunen P, Elomaa I. Adjuvant clodronate treatment does not reduce the frequency of skeletal metastases in node-positive breast cancer patients: 5-year results of a randomized controlled trial. J Clin Oncol. 2001;19:10–7.PubMed
67.
Paget S. The distribution of secondary growths in cancer of the breast. 1889. Cancer Metastasis Rev. 1989;8:98–101.PubMed
68.
Coleman R, De Boer R, Eidtmann H, Liombart A, Davidson N, Neven P, et al. Zoledronic acid (zoledronate) for postmenopausal women with early breast cancer receiving adjuvant letrozole (ZO-FAST study): final 60-month results. Ann Oncol. 2013;24:398–405.CrossRefPubMed
69.
Gnant M, Mlineritsch B, Stoeger H, Luschin-Ebengreuth G, Heck D, Menzel C, et al. Adjuvant endocrine therapy plus zoledronic acid in premenopausal women with early-stage breast cancer: 62-month follow-up from the ABCSG-12 randomised trial. Lancet Oncol. 2011;12:631–41.CrossRefPubMed
70.
Coleman RE, Marshall H, Cameron D, Dodwell D, Burkinshaw R, Keane M, et al. Breast cancer adjuvant therapy with zoledronic acid. N Engl J Med. 2011;365:1396–405.CrossRefPubMed
71.
Early Breast Cancer Trialists’ Collaborative Group, Coleman R, Powles T, Paterson A, Gnant M, Anderson S, et al. Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials. Lancet. 2015;386:1353–61.CrossRef
72.
Early Breast Cancer Trialists’ Collaborative Group, Peto R, Davies C, Godwin J, Gray R, Pan HC, et al. Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet. 2012;379:432–44.CrossRef
73.
Cox TR, Rumney RMH, Schoof EM, Perryman L, Høye AM, Agrawal A, et al. The hypoxic cancer secretome induces pre-metastatic bone lesions through lysyl oxidase. Nature. 2015;522:106–10.CrossRefPubMedPubMedCentral
74.
Gnant M, Pfeiler G, Dubsky PC, Hubalek M, Greil R, Jakesz R, et al. Adjuvant denosumab in breast cancer (ABCSG-18): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet. 2015;386:433–43.CrossRefPubMed
Metadata
Title
SEOM Clinical Guideline for bone metastases from solid tumours (2016)
Authors
C. Grávalos
C. Rodríguez
A. Sabino
M. Á. Seguí
J. A. Virizuela
A. Carmona
J. Cassinello
D. Isla
C. Jara
M. Martín
Publication date
01-12-2016
Publisher
Springer International Publishing
Published in
Clinical and Translational Oncology / Issue 12/2016
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-016-1590-1

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