Metastatik Kemik Ağrısının Palyasyonunda Nükleer Tıbbın Rolü
Özet
Kemik metastazına bağlı dirençli kemik ağrısı multidisipliner yaklaşımlarla yönetilen zorlu bir konudur Ağrılı kemik metastazlarının tedavisinde radyonüklitlerin kullanımı, ağrıya neden olan metastatik odakların hedeflenmesi ve radyofarmasötiklerin sistemik yolla iletilmesi prensibine dayanmaktadır. Nükleer tıpta radyonüklitlerle ağrının hafifletilmesi, osteoblastik metastazları hedef aldığından en sık osteoblastik metastaz yapma potansiyeli olan prostat ve meme kanserli hastalarda kullanılmaktadır. Kemik metastazını hedeflemek için kullanılan radyofarmasötikler arasında beta yayan rasyonüklidler olan 32P, 89Sr, 153Sm, 153Sm- EDTMP, 186Re-HEDP ve 188Re-HEDP, 177Lu-EDTMP ve ayrıca alfa yayan bir radyofarmasötik olan 223 RaCl2 yer alır. Beta yayıcılar, metastatik hastalıkta kemik ağrısının hafifletilmesi için uzun yıllardan beri kullanılmaktadır. 223RaCl2’nin kullanımı ise şu anda visseral metastazı olmayan semptomatik kastrasyon dirençli prostat kanserli hastalarla sınırlıdır 223RaCl2 ağrıyı gidermek için kullanılan ve sağkalımı iyileştirdiği gösterilen tek radyofarmasötiktir. 223Ra dışındaki tüm radyonüklitlerin uzaklaştırılmasının ana yolu renal atılımdır; 223Ra ise gastrointestinal atılım yoluyla elimine edilir. Beta yayan radyofarmasötiklerin en önemli yan etkisi hematolojik toksisitedir. bazı ajanlara spesifik olarak kusma, mide bulantısı ve ishal gibi gastrointestinal semptomlar izlenebilen diğer hematolojik olmayan yan etkilerdendir. Myelosupresyon, hamilelik ve emzirme mutlak kontrendikasyonlardır. Spinal kord basısı ve patolojik fraktürü olan hastalarda öncelikli tedavi olarak düşünülmemelidir.
Resistant bone pain due to bone metastasis is a challenging issue managed with multidisciplinary approaches. The use of radionuclides in the treatment of painful bone metastases is based on the principle of targeting the metastatic foci that cause pain and delivering radiopharmaceuticals systemically. In nuclear medicine, pain relief with radionuclides is used most frequently in prostate and breast cancer patients with the potential for osteoblastic metastases, as it targets osteoblastic metastases. Radiopharmaceuticals used to target bone metastasis include 32P, 89Sr, 153Sm, 153Sm-EDTMP, 186Re-HEDP and 188Re- HEDP, 177Lu-EDTMP, which are beta-emitting ratioclides, as well as 223 RaCl2, an alpha- emitting radiopharmaceutical. . 223RaCl2 is the only radiopharmaceutical used to relieve pain and has been shown to improve survival , The use of 223RaCl2 is currently limited to patients with symptomatic castration-resistant prostate cancer without visceral metastases. The main means of removal of all radionuclides except 223Ra is renal excretion; 223Ra is eliminated through gastrointestinal excretion. The most important side effect of beta-emitting radiopharmaceuticals is hematological toxicity. Gastrointestinal symptoms such as vomiting, nausea and diarrhea, specific to some agents, are other non-hematological side effects that can be observed. Myelosuppression, pregnancy and breastfeeding are absolute contraindications It should not be considered as a priority treatment in patients with spinal cord compression and pathological fracture.
Referanslar
Nielsen OS, Munro AJ, Tannock IF. Bone metastases: pathophysiology and management policy. J Clin Oncol. 1991;9:509–524.
Li, S, Peng, Y, Weinhandl, E.D,. et.al. Estimated number of prevalent cases of metastatic bone disease in the US adult population. Clin. Epidemiol. 2012, 4, 87.
Maini CL, Sciuto R, Romano L, et al. Radionuclide therapy with bone seeking radionuclides in palliation of painful bone metastases. J. Exp Clin Cancer Res 2003;22(Suppl 4):71-4
Bodei L, Lam M, Chiesa C, et al. EANM procedure guideline for treatment of refractory metastatic bone pain. Eur J Nucl Med Mol Imaging 2008;35(10):1934–40.
Barnes EA. Radiopharmaceuticals for painful bone metastases: perspective from radiation oncology. J Support Oncol. 2011;9:208–9
Porter AT, McEwan AJ, Powe JE, et al. Results of a randomized phase III trial to evaluate the efficacy of strontium-89 adjuvant to local field external beam irradiation in themanagement of endocrine resistant metastatic prostate cancer. Int J Radiat Oncol Biol Phys. 1993;25:805–13.
Tu SM, Millikan RE, Mengistu B, et al. Bone targeted therapy for advanced androgen in dependent carcinoma of the prostate: a randomised phase II trial. Lancet. 2001;357:336–41. 9.
Sciuto R, Festa A, Rea S, et al. Effects of low-dose cisplatin on strontium-89 therapy for painful bone metastases from prostate cancer: a randomized clinical trial. J Nucl Med. 2002;43:79–86.)
Manafi-Farid R, Masoumi F, Divband G , et al. Targeted Palliative Radionuclide Therapy for Metastatic Bone Pain J Clin Med 2020 Aug 12;9(8):2622
Elboğa U, Selçuk.NA. Ağrı Palyasyonunda Radyonüklit Tedavi. Nucl Med Semin 2020;6:423-435
Handkiewicz-Junak D, Poeppel TD, Bodei L, et al. EANM guidelines for radionuclide therapy of bone metastases with beta-emitting radionuclides. Eur J Nucl Med Mol Imaging 2018;45:846-859.
. Pantel AR., Eiber M,. Beyder, dd, et al. SNMMI Procedure Standard/EANM Practice Guideline for Palliative Nuclear Medicine Therapies of Bone Metastases J of Nuclear Medicine Technology, first published online June 14, 2023 as doi:10.2967/jnmt.123.265936
Paes FM, Serafini AN. Systemic metabolic radiopharmaceutical therapy in the treatment of metastatic bone pain Semin Nucl Med. 2010 Mar;40(2):89-104.
Pandit-Taskar, N., Larson, S. M., & Carrasquillo, J. A. Bone-seeking radiopharmaceuticals for treatment of osseous metastases, Part 1: α therapy with 223Ra-dichloride. J Nucl Med, (2014); 55(2), 268-274.
Silberstein EB, Williams C. Strontium-89 therapy for the pain of osseous metastases. J Nucl Med 1985;26(4):345–8.
Lewington VJ. Bone-seeking radionuclides for therapy. J Nucl Med 2005;46 Suppl 1:38s–47s.
.Finlay IG, Mason MD, Shelley M. Radioisotopes for the palliation of metastatic bone cancer: a systematic review. Lancet Oncol 2005;6(6):392–400.
Şanlı Y. Radionuclide Therapy in the Treatment of Bone Metastases. Turk J Oncol 2021;36(Supp 1):48–53
Askari E , Harsini S, Vahidfar N, et al. 177Lu-EDTMP for Metastatic Bone Pain Palliation: A Systematic Review and Meta-Analysis. Cancer Biother Radiopharm 2021 Jun;36(5):383-390.
Alavi M, Omidvari S, Mehdizadeh A, et al. Metastatic bone pain palliation using 177Lu-ethylenediaminetetramethylene phosphonic acid. World J Nucl Med 2015;14:109.
Dizdarevic S, Petersen PM, Essler M et al. Interim analysis of the REASSURE (Radium-223 alpha Emitter Agent in nonintervention Safety Study in mCRPC popUlation for ong-teRm Evaluation) study: patient characteristic and safety according to prior use of chemotherapy in routine clinical practice. Eur J Nucl Med Mol Imaging 2019;46(5):1102–10.
Castello A, Macapinlac HA, Lopci E et al. Prostate-specific antigen flare induced by (223) RaCl(2) in patients with metastatic castration-resistant prostate cancer. Eur J Nucl Med Mol Imaging 2018;45(13):2256–63.
Özdemir E. Prostat Kanserinin Ağrılı Kemik Metastazlarında Radyum-223 ile Radyonüklid Tedavi. Nucl Med Semin 2023;9(2):116-123
Parker C, Nilsson S, Heinrich D et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369:213–223.
Battal H, Erdoğan S. The Role of Radiopharmaceuticals in the Bone Metastases Therapy FABAD J. Pharm. Sci., 48, 2, 319-336, 2023
Thapa P, Nikam D, Das T, et al.. Clinical Efficacy and Safety Comparison of 177Lu-EDTMP with 153Sm-EDTMP on an Equidose Basis in Patients with Painful Skeletal Metastases. J Nucl Med 2015; 56:1513–1519.
Poeppel TD, Handkiewicz-Junak D, Andreeff M, et al. EANM guideline for radionuclide therapy with radium-223 of metastatic castration-resistant prostate cancer. Eur J Nucl Med Mol Imaging 2018;45:824-845.
Xofigo (radium Ra 223 dichloride). Package insert. Bayer Healthcare. U.S. Food and Drug Administration website. Revised December 2019. Accessed November 9, 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/203971s016lbl.pdf
Schaeffer E, Srinivas S, An Y. Prostate Cancer, Version 1.2023, NCCN Clinical Practice Guidelines in Oncology. National Comprehensive Cancer Network https://www nccn org/professionals/physician_gls/pdf/prostate pdf Accessed 2022.
Morris MJ, Corey E, Guise TA, et al. Radium-223 mechanism of action: implications for use in treatment combinations. Nat Rev Urol 2019;16:745-756.
Referanslar
Nielsen OS, Munro AJ, Tannock IF. Bone metastases: pathophysiology and management policy. J Clin Oncol. 1991;9:509–524.
Li, S, Peng, Y, Weinhandl, E.D,. et.al. Estimated number of prevalent cases of metastatic bone disease in the US adult population. Clin. Epidemiol. 2012, 4, 87.
Maini CL, Sciuto R, Romano L, et al. Radionuclide therapy with bone seeking radionuclides in palliation of painful bone metastases. J. Exp Clin Cancer Res 2003;22(Suppl 4):71-4
Bodei L, Lam M, Chiesa C, et al. EANM procedure guideline for treatment of refractory metastatic bone pain. Eur J Nucl Med Mol Imaging 2008;35(10):1934–40.
Barnes EA. Radiopharmaceuticals for painful bone metastases: perspective from radiation oncology. J Support Oncol. 2011;9:208–9
Porter AT, McEwan AJ, Powe JE, et al. Results of a randomized phase III trial to evaluate the efficacy of strontium-89 adjuvant to local field external beam irradiation in themanagement of endocrine resistant metastatic prostate cancer. Int J Radiat Oncol Biol Phys. 1993;25:805–13.
Tu SM, Millikan RE, Mengistu B, et al. Bone targeted therapy for advanced androgen in dependent carcinoma of the prostate: a randomised phase II trial. Lancet. 2001;357:336–41. 9.
Sciuto R, Festa A, Rea S, et al. Effects of low-dose cisplatin on strontium-89 therapy for painful bone metastases from prostate cancer: a randomized clinical trial. J Nucl Med. 2002;43:79–86.)
Manafi-Farid R, Masoumi F, Divband G , et al. Targeted Palliative Radionuclide Therapy for Metastatic Bone Pain J Clin Med 2020 Aug 12;9(8):2622
Elboğa U, Selçuk.NA. Ağrı Palyasyonunda Radyonüklit Tedavi. Nucl Med Semin 2020;6:423-435
Handkiewicz-Junak D, Poeppel TD, Bodei L, et al. EANM guidelines for radionuclide therapy of bone metastases with beta-emitting radionuclides. Eur J Nucl Med Mol Imaging 2018;45:846-859.
. Pantel AR., Eiber M,. Beyder, dd, et al. SNMMI Procedure Standard/EANM Practice Guideline for Palliative Nuclear Medicine Therapies of Bone Metastases J of Nuclear Medicine Technology, first published online June 14, 2023 as doi:10.2967/jnmt.123.265936
Paes FM, Serafini AN. Systemic metabolic radiopharmaceutical therapy in the treatment of metastatic bone pain Semin Nucl Med. 2010 Mar;40(2):89-104.
Pandit-Taskar, N., Larson, S. M., & Carrasquillo, J. A. Bone-seeking radiopharmaceuticals for treatment of osseous metastases, Part 1: α therapy with 223Ra-dichloride. J Nucl Med, (2014); 55(2), 268-274.
Silberstein EB, Williams C. Strontium-89 therapy for the pain of osseous metastases. J Nucl Med 1985;26(4):345–8.
Lewington VJ. Bone-seeking radionuclides for therapy. J Nucl Med 2005;46 Suppl 1:38s–47s.
.Finlay IG, Mason MD, Shelley M. Radioisotopes for the palliation of metastatic bone cancer: a systematic review. Lancet Oncol 2005;6(6):392–400.
Şanlı Y. Radionuclide Therapy in the Treatment of Bone Metastases. Turk J Oncol 2021;36(Supp 1):48–53
Askari E , Harsini S, Vahidfar N, et al. 177Lu-EDTMP for Metastatic Bone Pain Palliation: A Systematic Review and Meta-Analysis. Cancer Biother Radiopharm 2021 Jun;36(5):383-390.
Alavi M, Omidvari S, Mehdizadeh A, et al. Metastatic bone pain palliation using 177Lu-ethylenediaminetetramethylene phosphonic acid. World J Nucl Med 2015;14:109.
Dizdarevic S, Petersen PM, Essler M et al. Interim analysis of the REASSURE (Radium-223 alpha Emitter Agent in nonintervention Safety Study in mCRPC popUlation for ong-teRm Evaluation) study: patient characteristic and safety according to prior use of chemotherapy in routine clinical practice. Eur J Nucl Med Mol Imaging 2019;46(5):1102–10.
Castello A, Macapinlac HA, Lopci E et al. Prostate-specific antigen flare induced by (223) RaCl(2) in patients with metastatic castration-resistant prostate cancer. Eur J Nucl Med Mol Imaging 2018;45(13):2256–63.
Özdemir E. Prostat Kanserinin Ağrılı Kemik Metastazlarında Radyum-223 ile Radyonüklid Tedavi. Nucl Med Semin 2023;9(2):116-123
Parker C, Nilsson S, Heinrich D et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369:213–223.
Battal H, Erdoğan S. The Role of Radiopharmaceuticals in the Bone Metastases Therapy FABAD J. Pharm. Sci., 48, 2, 319-336, 2023
Thapa P, Nikam D, Das T, et al.. Clinical Efficacy and Safety Comparison of 177Lu-EDTMP with 153Sm-EDTMP on an Equidose Basis in Patients with Painful Skeletal Metastases. J Nucl Med 2015; 56:1513–1519.
Poeppel TD, Handkiewicz-Junak D, Andreeff M, et al. EANM guideline for radionuclide therapy with radium-223 of metastatic castration-resistant prostate cancer. Eur J Nucl Med Mol Imaging 2018;45:824-845.
Xofigo (radium Ra 223 dichloride). Package insert. Bayer Healthcare. U.S. Food and Drug Administration website. Revised December 2019. Accessed November 9, 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/203971s016lbl.pdf
Schaeffer E, Srinivas S, An Y. Prostate Cancer, Version 1.2023, NCCN Clinical Practice Guidelines in Oncology. National Comprehensive Cancer Network https://www nccn org/professionals/physician_gls/pdf/prostate pdf Accessed 2022.
Morris MJ, Corey E, Guise TA, et al. Radium-223 mechanism of action: implications for use in treatment combinations. Nat Rev Urol 2019;16:745-756.
