DOI QR코드

DOI QR Code

The Radiopharmaceutical Therapy for Multiple Bone Metastases of Cancer

암의 다발성 뼈 전이의 방사성동위원소 치료

  • Choi, Sang Gyu (Department of Radiation Oncology, Dankook University College of Medicine)
  • 최상규 (단국대학교 의과대학 방사선종양학교실)
  • Received : 2014.10.27
  • Accepted : 2014.11.18
  • Published : 2014.12.01

Abstract

Multiple bone metastases are common manifestation of many malignant tumors such as lung cancer, breast cancer, prostate cancer and renal cell carcinoma. Bone metastasis is secondary cancer in the bone, and it can lead to bone pain, fracture, and instability of the weight bearing bones, all of which may profoundly reduce physical activity and life quality. Treatment for bone metastasis is determined by multiple factors including pathology, performance status, involved site, and neurologic status. Treatment strategies for bone metastasis are analgesics, surgery, chemotherapy and radiotherapy. External beam radiotherapy has traditionally been an effective palliative treatment for localized painful bone metastasis. However, in some cases such as multiple bone metastases, especially osteoblastic bone metastasis originated from breast or prostate cancer, the radiopharmaceutical therapy using $^{89}Sr$, $^{186}Re$, $^{188}Re$, $^{153}Sm$ and $^{117m}Sn$ are also useful treatment option because of administrative simplicity (injection), few side effects, low risk of radiation exposure and high response rate. This article offers a concise explanation of the radiopharmaceutical therapy for multiple bone metastases.

암의 다발성 뼈 전이는 폐암, 유방암, 전립선암, 신장암 등 다양한 암에서 흔히 관찰된다. 뼈 전이는 뼈에 발생한 이차적인 암으로 통증, 골절, 그리고 체중을 지지하는 뼈의 불안정성을 유발할 수 있어 신체활동과 삶의 질을 저하시킨다. 뼈 전이 치료 시 병리조직소견, 환자의 전신 상태, 침범 부위, 그리고 환자의 신경학적 소견등 다양한 요인을 고려하여 진통제, 수술, 항암화학요법 그리고 방사선 치료 등을 시행하게 된다. 외부 방사선 치료는 전통적으로 국소 뼈 전이로 인한 통증의 치료에 이용되어왔지만 특히 유방암이나 전립선암의 다발성 골형성 뼈 전이의 경우 $^{89}Sr$, $^{186}Re$, $^{188}Re$, $^{153}Sm$ and $^{117m}Sn$ 등의 방사성동위원소를 이용한 치료가 시행되고 있는데, 약제 투여의 간편함, 낮은 부작용, 방사능 피폭위험에서의 안전성, 높은 치료 반응 등 다양한 장점을 가진 치료로 임상에서의 유용성이 점차 증가되고 있다.

Keywords

References

  1. Coleman RE. Clinical features of metastatic bone disease and risk of skeletal morbidity. Clin Cancer Res 2006;12(20 Pt 2):6243s-6249s. https://doi.org/10.1158/1078-0432.CCR-06-0931
  2. Finlay IG, Mason MD, Shelley M. Radioisotopes for the palliation of metastatic bone cancer: a systematic review. Lancet Oncol 2005;6:392-400. https://doi.org/10.1016/S1470-2045(05)70206-0
  3. Pandit-Taskar N, Batraki M, Divgi CR. Radiopharmaceutical therapy for palliation of bone pain from osseous metastases. J Nucl Med 2004;45:1358-65.
  4. Coleman RE, Rubens RD. Bone metastases and breast cancer. Cancer Treat Rev 1985;12:251-70. https://doi.org/10.1016/0305-7372(85)90008-8
  5. Takahashi T, Nishimura K, Yamano T, Gika M. Role of palliative radiotherapy for bone metastasis. J Palliat Care Med 2014;4:171.
  6. Raisz LG. Physiology and pathophysiology of bone remodeling. Clin Chem 1999;45(8 Pt 2):1353-8.
  7. Parfitt AM. Bone remodeling, normal and abnormal: a biological basis for the understanding of cancer-related bone disease and its treatment. Can J Oncol 1995;5 Suppl 1:1-10.
  8. Guise TA, Mundy GR. Cancer and bone. Endocr Rev 1998:19: 18-54.
  9. Roodman GD. Mechanisms of bone metastasis. N Engl J Med 2004;350:1655-64. https://doi.org/10.1056/NEJMra030831
  10. Honore P1, Rogers SD, Schwei MJ, Salak-Johnson JL, Luger NM, Sabino MC, et al. Murine models of inflammatory, neuropathic and cancer pain each generates a unique set of neurochemical changes in the spinal cord and sensory neurons. Neuroscience 2000;98:585-98. https://doi.org/10.1016/S0306-4522(00)00110-X
  11. Treede RD, Meyer RA, Raja SN, Campbell JN. Peripheral and central mechanisms of cutaneous hyperalgesia. Prog Neurobiol 1992;38:397-421. https://doi.org/10.1016/0301-0082(92)90027-C
  12. Mantyh PW, Clohisy DR, Koltzenburg M, Hunt SP. Molecular mechanisms of cancer pain. Nat Rev Cancer 2002;2:201-9. https://doi.org/10.1038/nrc747
  13. Sabino MA, Mantyh PW. Pathophysiology of bone cancer pain. J Support Oncol 2005;3:15-24.
  14. Buga S, Sarria JE. The management of pain in metastatic bone disease. Cancer Control 2012;19:154-66. https://doi.org/10.1177/107327481201900210
  15. Hoskin PJ, Stratford MR, Folkes LK, Regan J, Yarnold JR. Effect of local radiotherapy for bone pain on urinary markers of osteoclast activity. Lancet 2000;355:1428-9. https://doi.org/10.1016/S0140-6736(00)02144-9
  16. Lin A, Ray ME. Targeted and systemic radiotherapy in the treatment of bone metastasis. Cancer Metastases Rev 2006;25: 669-75.
  17. Smith HS. Radiation-induced analgesia in painful osseous metastases. In : Proceedings at the Capital District Pain Conference. Albany, NY, October 2005.
  18. Emami B, Lyman J, Brown A, Coia L, Goitein M, Munzenrider JE, et al. Tolerance of normal tissue to therapeutic irradiation. Int J Radat Oncol Biol Phys 1991;21:109-22.
  19. Lutz S, Berk L, Chang E, Chow E, Hahn C, Hoskin P, et al. Palliative radiotherapy for bone metastases: an ASTRO evidencebased guideline. Int J Radiat Oncol Biol Phys 2011;79:965-76. https://doi.org/10.1016/j.ijrobp.2010.11.026
  20. Feyer PC, Steingraeber M. Radiotherapy of bone metastasis in breast cancer patients - current approaches. Breast Care (Basel) 2012;7:108-12. https://doi.org/10.1159/000338724
  21. Jeremic B, Shibamoto Y, Acimovic L, Milicic B, Milisavljevic S, Nikolic N, et al. A randomized trial of three single-dose radiation therapy regimens in the treatment of metastatic bone pain. Int J Radiat Oncol Biol Phys 1998;42:161-7.
  22. Hoskin PJ, Price P, Easton D, Regan J, Austin D, Palmer S, et al. A prospective randomised trial of 4 Gy or 8 Gy single doses in the treatment of metastatic bone pain. Radiother Oncol 1992;23:74-8. https://doi.org/10.1016/0167-8140(92)90338-U
  23. Steenland E, Leer JW, van Houwelingen H, Post WJ, van den Hout WB, Kievit J, et al. 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 1999;52:101-9. https://doi.org/10.1016/S0167-8140(99)00110-3
  24. Hartsell WF, Scott CB, Bruner DW, Scarantino CW, Ivker RA, Roach M 3rd, et al. Randomized trial of short-versus long-course radiotherapy for palliation of painful bone metastases. J Natl Cancer Inst 2005;97:798-804. https://doi.org/10.1093/jnci/dji139
  25. The Bone Trial Working Party. 8 Gy single fraction radiotherapy for the treatment of metastatic skeletal pain: randomised comparison with a multifraction schedule over 12 months of patient follow-up. Bone Pain Trial Working Party. Radiother Oncol 1999;52:111-21. https://doi.org/10.1016/S0167-8140(99)00097-3
  26. Roos DE, Turner SL, O'Brien PC, Smith JG, Spry NA, Burmeister BH, et al. 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 2005;75:54-63. https://doi.org/10.1016/j.radonc.2004.09.017
  27. Kaasa S, Brenne E, Lund JA, Fayers P, Falkmer U, Holmberg M, et al. Prospective randomised multicenter trial on single fraction radiotherapy (8 Gy x 1) versus multiple fractions (3 Gy x 10) in the treatment of painful bone metastases. Radiother Oncol 2006;79:278-84. https://doi.org/10.1016/j.radonc.2006.05.006
  28. Foro Arnalot P, Fontanals AV, Galceran JC, Lynd F, Latiesas XS, de Dios NR, et al. 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 2008;89:150-5. https://doi.org/10.1016/j.radonc.2008.05.018
  29. Amouzegar-Hashemi F, Behrouzi H, Kazemian A, Zarpak B, Haddad P. Single versus multiple fractions of palliative radiotherapy for bone metastases: a randomized clinical trial in Iranian patients. Curr Oncol 2008;15:151.
  30. van den Hout WB, van der Linden YM, Steenland E, Wiggenraad RG, Kievit J, de Haes H, et al. Single-versus multiple-fraction radiotherapy in patients with painful bone metastases: cost-utility analysis based on a randomized trial. J Natl Cancer Inst 2003; 95:222-9. https://doi.org/10.1093/jnci/95.3.222
  31. Salazar OM, Rubin P, Keller B, Scarantino C. Systemic (half-body) radiation therapy: response and toxicity. Int J Radiat Oncol Biol Phys 1978;4:937-50. https://doi.org/10.1016/0360-3016(78)90003-2
  32. Salazar OM, Sandhu T, da Motta NW, Perez Escutia MA, Lanzos-Gonzales E, Mouelle-Sone A, et al. Fractionated half-body irradiation (HBI) for the rapid palliation of widespread, symptomatic, metastatic bone disease: a randomized Phase III trial of the International Atomic Energy Agency (IAEA). Int J Radiat Oncol Biol Phys 2001;50:765-75. https://doi.org/10.1016/S0360-3016(01)01495-X
  33. Salazar OM, Rubin P, Hendrickson FR, Komaki R, Poulter C, Newall J, et al. Single-dose half-body irradiation for palliation of multiple bone metastases from solid tumors. Final Radiation Therapy Oncology Group report. Cancer 1986;58:29-36. https://doi.org/10.1002/1097-0142(19860701)58:1<29::AID-CNCR2820580107>3.0.CO;2-2
  34. Zelefsky MJ, Scher HI, Forman JD, Linares LA, Curley T, Fuks Z. Palliative hemiskeletal irradiation for widespread metastatic prostate cancer: a comparison of single dose and fractionated regimens. Int J Radiat Oncol Biol Phys 1989;17:1281-5. https://doi.org/10.1016/0360-3016(89)90537-3
  35. Poulter CA, Cosmatos D, Rubin P, Urtasun R, Cooper JS, Kuske RR, et al. A report of RTOG 8206: a phase III study of whether the addition of single dose hemibody irradiation to standard fractionated local field irradiation is more effective than local field irradiation alone in the treatment of symptomatic osseous metastases. Int J Radiat Oncol Biol Phys. 1992;23:207-14. https://doi.org/10.1016/0360-3016(92)90563-W
  36. Glaser MG, Howard N, Waterfall N. Carcinoma of the prostate: the treatment of bone metastases by radiophosphorus. Clin Radiol 1981;32:695-7. https://doi.org/10.1016/S0009-9260(81)80342-X
  37. Taymor ML, McArthur JW, Ingersoll FM. The effect of interstitial cell stimulating hormone upon the uptake of P32 in the rat prostate. Surg Forum 1953;(38th Congress):317-21.
  38. Schmidt CG, Firusian N. 89-Sr for the treatment of incurable pain in patient with neoplastic osseous infiltrations. Int J Clin Pharmacol 1974;7:199-205.
  39. Silberstein EB, Williams C. Strontium-89 therapy for the pain of osseous metastases. J Nucl Med 1985;26:345-8.
  40. Lass P. Radionuclide treatment of bone metastases - current concepts and trends. Nucl Med Rev Cent East Eur 2001;4:1-3.
  41. Horvat AG, Kovac V, Strojan P. Radiotherapy in palliative treatment of painful bone metastases. Radiol Oncol 2009;43:213-24.
  42. Blake GM, Zivanovic MA, Blaquiere RM, Fine DR, McEwan AJ, Ackery DM. Strontium-89 therapy: measurement of absorbed dose to skeletal metastases. J Nucl Med 1988;29:549-57.
  43. Blake GM, Zivanovic MA, McEwan AJ, Ackery DM. Sr-89 therapy: strontium kinetics in disseminated carcinoma of the prostate. Eur J Nucl Med 1986;12:447-54.
  44. Laing AH1, Ackery DM, Bayly RJ, Buchanan RB, Lewington VJ, McEwan AJ, et al. Strontium-89 chloride for pain palliation in prostatic skeletal malignancy. Br J Radiol 1991;64:816-22. https://doi.org/10.1259/0007-1285-64-765-816
  45. Mertens WC, Stitt L, Porter AT. Strontium 89 therapy and relief of pain in patients with prostatic carcinoma metastatic to bone: a dose response relationship? Am J Clin Oncol 1993;16:238-42. https://doi.org/10.1097/00000421-199306000-00009
  46. Sciuto R, Festa A, Rea S, Pasqualoni R, Bergomi S, Petrilli G, et al. Effects of low-dose cisplatin on 89Sr therapy for painful bone metastases from prostate cancer: a randomized clinical trial. J Nucl Med 2002;43:79-86.
  47. Porter AT, McEwan AJ. Strontium-89 as an adjuvant to external beam radiation improves pain relief and delays disease progression in advanced prostate cancer: results of a randomized controlled trial. Semin Oncol 1993;20(3 Suppl 2):38-43.
  48. Oosterhof GO, Roberts JT, de Reijke TM, Engelholm SA, Horenblas S, von der Maase H, et al. Strontium(89) chloride versus palliative local field radiotherapy in patients with hormonal escaped prostate cancer: a phase III study of the European Organisation for Research and Treatment of Cancer, Genitourinary Group. Eur Urol 2003;44:519-26. https://doi.org/10.1016/S0302-2838(03)00364-6
  49. Henk G. van der Poel. Radionuclide treatment in metastasized prostate cancer. EAU-EBU Update Series 5 2007;113-25. https://doi.org/10.1016/j.eeus.2007.02.002
  50. Silberstein EB. Teletherapy and radiopharmaceutical therapy of painful bone metastases. Semin Nucl Med 2005;35:152-8.
  51. de Klerk JM, Zonnenberg BA, van het Schip AD, van Dijk A, Han SH, Quirijnen JM, et al. Dose escalation study of rhenium-186 hydroxyethylidene diphosphonate in patients with metastatic prostate cancer. Eur J Nucl Med 1994;21:1114-20. https://doi.org/10.1007/BF00181067
  52. de Klerk JM, van het Schip AD, Zonnenberg BA, van Dijk A, Quirijnen JM, Blijham GH, et al. Phase 1 study of rhenium- 186-HEDP in patients with bone metastases originating from breast cancer. J Nucl Med 1996;37:244-9.
  53. Han SH, Zonneberg BA, de Klerk JM, Quirijnen JM, van het Schip AD, van Dijk A, et al. 186Re-etidronate in breast cancer patients with metastatic bone pain. J Nucl Med 1999;40:639-42.
  54. O'Sullivan JM, Norman AR, McCready VR, Flux G, Buffa FM, Johnson B, et al. A phase 2 study of high-activity 186Re-HEDP with autologous peripheral blood stem cell transplant in progressive hormone-refractory prostate cancer metastatic to bone. Eur J Nucl Med Mol Imaging 2006;33:1055-61. https://doi.org/10.1007/s00259-005-0010-5
  55. Liepe K, Kropp J, Runge R, Kotzerke J. Therapeutic efficiency of rhenium-188-HEDP in human prostate cancer skeletal metastases. Br J Cancer 2003;89:625-9. https://doi.org/10.1038/sj.bjc.6601158
  56. Palmedo H, Manka-Waluch A, Albers P, Schmidt-Wolf IG, Reinhardt M, Ezziddin S, et al. Repeated bone-targeted therapy for hormone-refractory prostate carcinoma: tandomized phase II trial with the new, high-energy radiopharmaceutical rhenium-188 hydroxyethylidenediphosphonate. .J Clin Oncol 2003;21:2869-75. https://doi.org/10.1200/JCO.2003.12.060
  57. Goeckeler WF, Troutner DE, Volkert WA, Edwards B, Simon J, Wilson D. 153Sm radiotherapeutic bone agents. Int J Rad Appl Instrum B 1986;13:479-82. https://doi.org/10.1016/0883-2897(86)90028-0
  58. Paes FM, Ernani V, Hosein P, Serafini AN. Radiopharmaceuticals: when and how to use them to treat metastatic bone pain. J Support Oncol 2011;9:197-205. https://doi.org/10.1016/j.suponc.2011.06.004
  59. Holmes RA. [153Sm]EDTMP: a potential therapy for bone cancer pain. Semin Nucl Med 1992;22:41-5.
  60. Collins C, Eary JF, Donaldson G, Vernon C, Bush NE, Petersdorf S, et al. Samarium-153-EDTMP in bone metastases of hormone refractory prostate carcinoma: A phase I/II trial. J Nucl Med 1993;34:1839-44.
  61. Resche I, Chatal JF, Pecking A, Ell P, Duchesne G, Rubens R, et al. A dose-controlled study of 153Sm-ethylenediaminetetramethylenephosphonate (EDTMP) in the treatment of patients with painful bone metastases. Eur J Cancer 1997;33:1583-91. https://doi.org/10.1016/S0959-8049(97)00155-X
  62. Turner JH, Claringbold PG, Hetherington EL, Sorby P, Martindale AA. A phase I study of samarium-153 ethylenediaminetetramethylene phosphonate therapy for disseminated skeletal metastases. J Clin Oncool 1989;7:1926-31. https://doi.org/10.1200/JCO.1989.7.12.1926
  63. Lewington VJ. Bone-seeking radionuclides for therapy. J Nucl Med 2005;46 Suppl 1:38S-47S.
  64. Srivastava SC, Atkins HL, Krishnamurthy GT, Zanzi I, Silberstein EB, Meinken G, et al. Treatment of metastatic bone pain with tin-117m Stannic diethylenetriaminepentaacetic acid: a phase I/II clinical study. Clin Cancer Res 1998;4:61-8.
  65. Liu, C; Brasic JR, Liu X, Li H, Xiang X, Luo Z, et al. Timing and optimized acquisition parameters for the whole-body imaging of $^{177}Lu-EDTMP$ toward performing bone palliation treatment. Nucl Med Commun 2012;33:90-6. https://doi.org/10.1097/MNM.0b013e32834d3c13
  66. Safarzadeh L. (175)Yb-TTHMP as a good candidate for bone pain palliation and substitute of other radiopharmaceuticals. Indian J Nucl Med 2014;29:135-9. https://doi.org/10.4103/0972-3919.136555
  67. Das T, Chakraborthy S, Sarma HD, Tandon P, Banerjee S, Venkatesh M, et al. $^{177}Tm-EDTMP$: a potential cost effective alternative to $^{89}SrC_{l2}$ for bone pain palliation. Nucl Med Biol 2009;36:561-8. https://doi.org/10.1016/j.nucmedbio.2009.02.002