Abstract
Bone is one of the most common sites of metastasis. This chapter addresses three notable issues for bone metastases patients receiving radiotherapy: prognosis, complications affecting this patient population and predictive factors for various toxicities. Overall survival estimates for bone metastases patients have improved considerably over the past 50 years and vary with respect to primary tumour location. Numerous general and tumour-specific predictors influence survival in this patient population; when combined, these covariates have been used to develop relevant predictive models for survival. Toxicities in bone metastases patients are generally mild, and risk is determined by radiation site and dose. One noteworthy toxicity that has garnered significant research in recent years is radiotherapy-induced nausea and vomiting, for which risk factors include the anatomic site being irradiated, a greater radiotherapy field size, a female gender and anxiety. Complications that may affect bone metastases patients are spinal cord compression, impending or pathologic fractures, neuropathic pain and recurrence of bone metastasis. In closing, this chapter contains essential information that should be considered in the delivery of treatment; ultimately, however, treatment choice should be tailored to the individual patient and should be based on a variety of clinical and sociodemographic factors.
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References
Abrahm JL, Banffy MB, Harris MB (2008) Spinal cord compression in patients with advanced metastatic cancer. J Am Med Assoc 299(8):937–946
Akimoto S et al (1999) Inability of bone turnover marker as a strong prognostic indicator in prostate cancer patients with bone metastasis: comparison with the extent of disease (EOD) grade. Prostate 38:28–34
Ali SM, Demers LM, Leitzel K, Harvey HA, Clemens D, Mallinak N et al (2004) Baseline serum NTx levels are prognostic in metastatic breast cancer patients with bone-only metastasis. Ann Oncol 15(3):455–459
Altundag MB, Ucer AR, Calikoglu T, Guran Z (2002) Single (500 cGy, 800 cGy) and multifraction (300 X 10 cGy) radiotherapy schedules in the treatment of painful bone metastases. Turk J Hematol Oncol 12:16–21
Amouzegar-Hashemi F, Behrouzi H, Kazemian A et al (2008) Single versus multiple fractions of palliative radiotherapy for bone metastases: a randomized clinical trial in Iranian patients. Curr Oncol 15:151
Bae HM, Lee SH, Kim TM, Kim DW, Yang SC, Wu HG, Kim YW, Heo DS (2012) Prognostic factors for non-small cell lung cancer with bone metastasis at the time of diagnosis. Lung Cancer 77(3):572–577
Basch E, Prestrud AA, Hesketh PJ et al (2011) Antiemetics: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 29(31):4189–4198
Berruti A, Cook R, Saad F, Buttigliero C, Lipton A, Tampellini M et al (2012) Prognostic role of serum parathyroid hormone levels in advanced prostate cancer patients undergoing zoledronic acid administration. Oncologist 17(5):645–652
Bone Pain Trial Working Party (1999) 8 Gy single fraction radiotherapy for the treatment of metastatic skeletal pain: randomized comparison with multi-fraction schedule over 12 months of patient follow-up. Radiother Oncol 52(2):111–121
Brasso K, Christensen IJ, Johansen JS, Teisner B, Garnero P, Price PA et al (2006) Prognostic value of PINP, bone alkaline phosphatase, CTX-I, and YKL-40 in patients with metastatic prostate carcinoma. Prostate 66(5):503–513
Brown JE, Cook RJ, Major P et al (2005) Bone turnover markers as predictors of skeletal complications in prostate cancer, lung cancer, and other solid tumors. J Natl Cancer Inst 97:59–69
Brown JE, Cook RJ, Lipton A, Coleman RE (2012) Serum lactate dehydrogenase is prognostic for survival in patients with bone metastases from breast cancer: a retrospective analysis in bisphosphonate-treated patients. Clin Cancer Res 18(22):6348–6355
Chow E, Fung KW, Panzarella T, Bezjak A, Danjoux C, Tannock I (2002) A predictive model for survival in metastatic cancer patients attending an outpatient palliative radiotherapy clinic. Int J Radiat Oncol Biol Phys 53(5):1291–1302
Chow E, Harris K, Fan G, Tsao M, Sze WM (2007) Palliative radiotherapy trials for bone metastases: a systematic review. J Clin Oncol 25(11):1423–1436
Chow E, Abdolell M, Panzarella T, Harris K, Bezjak A, Warde P, Tannock I (2008) Predictive model for survival in patients with advanced cancer. J Clin Oncol 26(36):5863–5869
Chow E, Abdolell M, Panzarella T, Harris K, Bezjak A, Warde P, Tannock I (2009) Validation of a predictive model for survival in metastatic cancer patients attending an outpatient palliative radiotherapy clinic. Int J Radiat Oncol Biol Phys 73(1):280–287
Chow E, Zeng L, Salvo N, Dennis K, Tsao M, Lutz S (2012) Update on the systemic review of palliative radiotherapy trials for bone metastases. Clin Oncol (R Coll Radiol) 24(2):112–124
Coates A, Abraham SK, Kaye SB (1983) On the receiving end: patient perception of the side effects of cancer chemotherapy. Eur J Cancer Clin Oncol 19:203
Cole D (1989) A randomized trial of a single treatment versus conventional fractionation in the palliative radiotherapy of painful bone metastases. Clin Oncol 1:59–62
Coleman RE (1997) Skeletal complications of malignancy. Cancer 80(8 Suppl):1588–1594
Coleman RE (2001) Metastatic bone disease: clinical features, pathophysiology and treatment strategies. Cancer Treat Rev 27:165–176
Coleman R, Rubens R (1987) The clinical course of bone metastases in breast cancer. Br J Cancer 77:336–340
Coleman RE, Smith P, Rubens RD (1998) Clinical course and prognostic factors following bone recurrence from breast cancer. Br J Cancer 77(2):336–340
Crawford E, Eisenberger M, McLeod K (1989) A controlled trial of leuprolide with and without flutamide in prostatic carcinoma. N Engl J Med 321:419–424
Danjoux CE, Rider WD, Fitzpatrick PJ (1979) The acute radiation syndrome. A memorial to William Michael Court–Brown. Clin Radiol 30:581–584
Dennis K, Maranzano E, De Angelis C et al (2011a) Radiotherapy-induced nausea and vomiting. Exp Rev Pharmacoecon Outcomes Res 11:685–692
Dennis K, Chow E, Roos D, DeAngelis C, Hartsell W, van der Linden Y, Hoskin P (2011b) Should bone metastases causing neuropathic pain be treated with single-dose radiotherapy? Clin Oncol 23(7):482–484
Eisenberger M, Crawford E, Wolf M (1994) Prognostic factors in stage D2 prostate cancer: important implications for future trials. Semin Oncol 21:613–619
El-Shenshawy H, Kandeel A, El-Essawy S (2006) The effect of a single fraction compared to multiple fractions radiotherapy on painful bone metastases with evaluation of computed tomography bone density in osteolytic bone metastases. Bull Alex Fac Med 42:439
Enblom A, Bergius AB, Steineck G, Hammar M, Borjeson S (2009) One third of patients with radiotherapy-induced nausea consider their antiemetic treatment insufficient. Support Care Cancer 17(1):23–32
Feyer PC, Stewart AL, Titlbach OJ (1998) Aetiology and prevention of emesis induced by radiotherapy. Support Care Cancer 6(3):253–260
Feyer PC, Maranzano E, Molassiotis A, Roila F, Clark-Snow RA, Jordan K (2011) Radiotherapy-induced nausea and vomiting (RINV): MASCC/ESMO guideline for antiemetics in radiotherapy: update 2009. Support Care Cancer 19(Suppl. 1):S5–S14
Foro P, Algara M, Reig A et al (1998) Randomized prospective trial comparing three schedules of palliative radiotherapy. Preliminary results. Oncologia 21:55–60
Foro P, Fontanals AV, Galceran JC et al (2008) Randomized clinical trial with two palliative radiotherapy regimens in painful bone metastases: 30 Gy in 10 fractions compared with 8 Gy in single fraction. Radiother Oncol 89:150–155
Galasko CSB (1986) Skeletal metastases. Butterworths, London
Gaze MN, Kelly CG, Kerr GR et al (1997) Pain relief and quality of life following radiotherapy for bone metastases: a randomized trial of two fractionation schedules. Radiother Oncol 45:109–116
Grond S, Radbruch L, Meuser T, Sabatowski R, Loick G, Lehmann KA (1999) Assessment and treatment of neuropathic cancer pain following WHO guidelines. Pain 79(1):15–20
Hamouda WE, Roshdy W, Teema M (2007) Single versus conventional fractionated radiotherapy in the palliation of painful bone metastases. Gulf J Oncol 1:35–41
Harada H, Katagiri H, Kamata M, Yoshioka Y, Asakura H, Hashimoto T, Furutani K, Takahashi M, Sakahara H, Nishimura T (2010) Radiological response and clinical outcome in patients with femoral bone metastases after radiotherapy. J Radiat Res 51(2):131–136
Harrington KD (1988) Prophylactic management of impending fractures. In: Harrington KD (ed) Orthopaedic management of metastatic bone disease. CV Mosby, St. Louis
Hartsell W et al (2005) Randomized trial of short versus long-course radiotherapy for palliation of painful bone metastases. J Natl Cancer Inst 97:798–804
Hatse S, Lambrechts D, Verstuyf A, Smeets A, Brouwers B, Vandorpe T et al (2012) Vitamin D status at breast cancer diagnosis: correlation with tumor characteristics, disease outcome, and genetic determinants of vitamin D insufficiency. Carcinogenesis 33(7):1319–1326
Holt T, Hoskin P, Maranzano E, Sahgal A, Schild SE, Ryu S, Loblaw A (2012) Malignant epidural spinal cord compression: the role of external beam radiotherapy. Curr Opin Support Palliat Care 6(1):103–108
Iordanidou L, Trivizaki E, Saranti S et al (2006) Is there a role of whole body bone scan in early stages of non small cell lung cancer patients. J Buon 11:491–497
Izumi K, Mizokami A, Itai S, Shima T, Shigehara K, Miwa S et al (2012) Increases in bone turnover marker levels at an early phase after starting zoledronic acid predicts skeletal-related events in patients with prostate cancer with bone metastasis. BJU Int 109(3):394–400
Jarvis GK, Northcott HC (1987) Religion and differences in morbidity and mortality. Soc Sci Med 25:813–824
Jawad MU, Scully SP (2010) In brief: classifications in brief: Mirels’ classification: metastatic disease in long bones and impending pathologic fracture. Clin Orthop Relat Res 468(10):2825–2827
Jung K, Lein M, Stephan C, Von Hosslin K, Semjonow A, Sinha P et al (2004) Comparison of 10 serum bone turnover markers in prostate carcinoma patients with bone metastatic spread: diagnostic and prognostic implications. Int J Cancer 111(5):783–791
Kaasa S, Brenne E, Lund J et al (2006) Prospective randomized multicentre trial on single fraction radiotherapy (8 Gy X 1) versus multiple fractions (3 Gy X 10) in the treatment of painful bone metastases: Phase III randomized trial. Radiother Oncol 79:278–284
Kagei K, Suzuki K, Shirato H et al (1990) A randomized trial of single and multifraction radiation therapy for bone metastasis: a preliminary report. Gan No Rinsho 36:2553–2558
Kerba M, Wu JS, Duan Q, Hagen NA, Bennett MI (2010) Neuropathic pain features in patients with bone metastases referred for palliative radiotherapy. J Clin Oncol 28(33):4892–4897
Komatsu T, Kunieda E, Oizumi Y, Tamai Y, Akiba T (2012) An analysis of the survival rate after radiotherapy in lung cancer patients with bone metastasis: is there an optimal subgroup to be treated with high-dose radiation therapy? Neoplasma 59(6):650–657
Kwok Y, Regine WF, Patchell RA (2005) Radiation therapy alone for spinal cord compression: time to improve upon a relatively ineffective status quo. J Clin Oncol 23(15):3308–3310
Landis S et al (1999) Cancer statistics. CA Cancer J Clin 49:8–29
Lipton A, Chapman JA, Demers L, Shepherd LE, Han L, Wilson CF et al (2011) Elevated bone turnover predicts for bone metastasis in postmenopausal breast cancer: results of NCIC CTG MA. 14. J Clin Oncol 29(27):3605–3610
Llobera J, Esteva M, Rifa J et al (2000) Terminal cancer: duration and prediction of survival time. Eur J Cancer 36:2036–2043
Lo SS, Holden L, Lutz ST, Liu RK, Chow E (2010) Should all patients with uncomplicated bone metastases be treated with a single 8-gy fraction? Exp Rev Pharmacoecon Outcomes Res 10(2):95–98
Loblaw DA, Perry J, Chambers A, Laperriere NJ (2005) Systematic review of the diagnosis and management of malignant extradural spinal cord compression: the cancer care Ontario practice guidelines initiative’s neuro-oncology disease site group. J Clin Oncol 23(9):2028–2037
Maltoni M, Caraceni A, Brunelli C et al (2005) Prognostic factors in advanced cancer patients: evidence-based clinical recommendations—a study by the steering committee of the European Association for Palliative Care. J Clin Oncol 23:6340–6348
Maranzano E, Bellavita R, Rossi R, DeAngelis V, Frattegiani A, Bagnoli R et al (2005) Short-course versus split-course radiotherapy in metastatic spinal cord compression: results of a phase III, randomized, multicenter trial. J Clin Oncol 23(15):3358–3365
Maranzano E, De Angelis V, Pergolizzi S et al (2010) A prospective observational trial on emesis in radiotherapy: analysis of 1020 patients recruited in 45 Italian radiation oncology centres. Radiother Oncol 94(1):36–41
Matzkin H, Perito P, Soloway M (1993) Prognostic factors in metastatic prostate cancer. Cancer 72(suppl 12):3788–3792
Morris PG, Ulaner GA, Eaton A et al (2012) Standardized uptake value by position emission tomography/computed tomography as a prognostic variable in metastatic breast cancer. Cancer 118(22):5454–5462
Nielson O et al (1998) Randomized trial of single dose versus fractionated palliative radiotherapy of bone metastases. Radiother Oncol 47:233–240
Ozsaran Z, Yalman D, Anacek Y et al (2001) Palliative radiotherapy in bone metastases: results of a randomized trial comparing three fractionation schedules. J Buon 6:43–48
Perez JE, Machiavelli M, Leone BA, Romero A, Rabinovich MG, Vallejo CT, Bianco A, Rodriguez R, Cuevas MA, Alvarez LA (1990) Bone-only versus visceral-only metastatic pattern in breast cancer: analysis of 150 patients. Am J Clin Oncol 13:294–298
Phillips DP, Smith DG (1990) Postponement of death until symbolically meaningful occasions. J Am Med Assoc 263:1947–1951
Plunkett TA, Rubens RD (2005) Clinical features and prognosis of bone metastases. In: Jasmin C, Coleman RE, Coia LR, Capanna R, Saillant G (eds) Textbook of bone metastases. Wiley, Chichester
Popovic M et al (2012) Comparing prognostic factors in patients with spinal metastases: a literature review. Exp Rev Pharmacoecon Outcomes Res 12(3):345–356
Price P, Hoskin PJ, Easton D et al (1986) Prospective randomized trial of single and multifraction radiotherapy schedules in the treatment of painful bony metastases. Radiother Oncol 6:247–255
Priestman TJ, Priestman SG (1984) An initial evaluation of Nabilone in the control of radiotherapy-induced nausea and vomiting. Clin Radiol 35(4):265–266
Priestman TJ, Roberts JT, Lucraft H et al (1990) Results of a randomized, double-blind comparative study of ondansetron and metoclopramide in the prevention of nausea and vomiting following high-dose upper abdominal irradiation. Clin Oncol 2(2):71–75
Rades D, Abrahm JL (2010) The role of radiotherapy for metastatic epidural spinal cord compression. Nat Rev Clin Oncol 7(10):590–598
Rades D, Fehlauer F, Schulte R, Veninga T, Stalpers LJ, Basic H et al (2006) Prognostic factors for local control and survival after radiotherapy of metastatic spinal cord compression. J Clin Oncol 24(21):3388–3393
Rades D, Rudat V, Veninga T, Stalpers LJ, Basic H, Karstens JH et al (2008) A score predicting post treatment ambulatory status in patients irradiated for metastatic spinal cord compression. Int J Radiat Oncol Biol Phys 72(3):905–908
Reuben DB, Mor V, Hiris J (1988) Clinical symptoms and length of survival in patients with terminal cancer. Arch Intern Med 148:1586–1591
Robson M, Dawson N (1996) How is androgen-dependent metastatic prostate cancer best treated? Hemat Oncol Clin North Am 10:727–747
Roos D et al (2005) Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic pain due to bone metastases (Trans-Tasman Radiation Oncology Group, TROG 96.05). Radiother Oncol 75:54–63
Rosen LS, Gordon D, Tchekmedyian S et al (2003) Zoledronic acid versus placebo in the treatment of skeletal metastases in patients with lung cancer and other solid tumors: a phase III, double-blind, randomized trial—the Zoledronic Acid Lung Cancer and Other Solid Tumors Study Group. J Clin Oncol 21:3150–3157
Ruggieri P, Mavrogenis AF, Casadei R, Errani C, Angelini A, Calabro T (2010) Protocol of surgical treatment of long bone pathologic fractures. Injury 41(11):1161–1167
Sabbatini P et al (1999) Prognostic significance of extent of disease in bone in patients with androgen-independent prostate cancer. J Clin Oncol 17:948–957
Sandler A, Gray R, Perry MC et al (2006) Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355:2542–2550
Sarkar SK, Sarkar S, Pahari B et al (2002) Multiple and single fraction palliative radiotherapy in bone secondaries: a prospective study. Ind J Radiol Imag 12:281–284
Schoenbach VJ, Kaplan BH, Fredman L et al (1986) Social ties and mortality in Evans County, Georgia. Am J Epidemiol 123:577–591
Sejpal SV, Bhate A, Small W (2007) Palliative radiation therapy in the management of brain metastases, spinal cord compression, and bone metastases. Semin Intervent Radiol 24(4):363–374
Shaham D, Breuer R, Copel L et al (2006) Computed tomography screening for lung cancer: applicability of an international protocol in a single-institution environment. Clin Lung Cancer 7:262–267
Shiue K, Sahgal A, Chow E, Lutz ST, Chang EL, Mayr NA et al (2010) Management of metastatic spinal cord compression. Expert Rev Anticancer Ther 10(5):697–708
Solomayer EF, Diel IJ, Meyberg GC, Gollan Ch, Bastert G (2000) Metastatic breast cancer: clinical course, prognosis and therapy related to the first site of metastases. Breast Cancer Res Treat 59:271–278
Soloway M, Hardeman S, Hickey D (1988) Stratification of patients with metastatic prostate cancer based on extent of disease on initial bone scan. Cancer 61:195–202
Steenland E et al (1999) The effect of a single fraction compared to multiple fractions on painful bone metastases: a global analysis of the Dutch Bone Metastasis Study. Radiother Oncol 52:101–109
The Italian Group for Antiemetic Research in Radiotherapy (1999) Radiation-induced emesis: a prospective observational multicenter Italian trial. Int J Radiat Oncol Biol Phys 44(3):619–625
Toscani F, Brunelli C (2005) Predicting survival in terminal cancer patients: clinical observation or quality-of-life evaluation? Palliat Med 19:220–227
Urch CE, Dickenson AH (2008) Neuropathic pain in cancer. Eur J Cancer 44(8):1091–1096
Wedin R (2001) Surgical treatment for pathologic fractures. Acta Orthop Scand 72(Suppl 302):1–29
Yamashita K, Ueda T, Komatsubara Y, Koyama H, Inaji H, Yonenobu K, Ono K (1991) Breast cancer with bone-only metastases: visceral metastases-free rate in relation to anatomic distribution of bone metastases. Cancer 68:634–637
Yamashita K, Ueda T, Komatsubara Y, Koyama H, Inaji H, Ono K, Yonenobu K (1992) A classification of bone metastases from breast cancer. In: Uchida A, Ono K (eds) Recent advances in musculoskeletal oncology. Springer, Berlin
Zhang L, Teng Y, Zhang Y et al (2012) Receptor activator for nuclear factor κ B expression predicts poor prognosis in breast cancer patients with bone metastasis but not in patients with visceral metastasis. J Clin Pathol 65:36–40
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Popovic, M. et al. (2013). Bone Metastases. In: Nieder, C., Gaspar, L. (eds) Decision Tools for Radiation Oncology. Medical Radiology(). Springer, Berlin, Heidelberg. https://doi.org/10.1007/174_2013_836
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