title: Radionuclide therapy and integrated protocols for bone metastases.
abstract: Bone metastases are responsible for most of the morbidity and mortality associated with solid malignant tumors, occurring in about 65-70% of the patients with advanced breast or prostate cancer. The pathophysiology of skeletal metastasis is a complex process that involves several biologic process leading to cellular invasion, adhesions and stimulation of osteoclasts and osteoblasts with the mediation of several factors including cytokines, serine proteases and tumor-derived factors. The clinical management of pain from bone metastasis, which is mostly due to indirect stimulation of sensory nerve endings by cytokines and other biologically-active compounds released locally in response to the presence of tumor cells in the bone marrow, includes several options that can be used either alone or in varying combinations, such as analgesic drugs, chemo- or hormonal therapy, bisphosponates, external beam radiation therapy, and surgery. Bone-seeking radiopharmaceuticals play an important role in the treatment of pain caused by multiple blastic or mixed-type skeletal lesions; they have in general a favorable toxicity profile and a high rate of overall clinical benefit, although they may differ in terms of duration of pain palliation and suitability for repeat treatments. The palliative effect can be attributed to the radiation targeted to the bone marrow space, and the overall average response ranges between about 45-80%, with complete response in 10-30% of the cases. In selected clinical conditions, radionuclide therapy can also constitute an effective systemic treatment beyond bone pain palliation, and a synergistic anti-tumour effect can be expected by the combination with other agents, such as chemotherapy or bisphosphonates. This review summarizes the current experience with bone-seeking radiopharmaceuticals used for bone pain palliation, focusing on indications, patients' selection, efficacy and toxicity. Finally, the available data on combination therapies showing encouraging results as to potential anti-tumor efficacy are also reviewed.
authors: Regional Center of Nuclear Medicine, University of Pisa Medical School, Pisa, Italy.
authors: S
authors: S
authors: Chiacchio
authors: S
authors: S
authors: Mazzarri
authors: A
authors: A
authors: Lorenzoni
authors: N
authors: N
authors: Nyakale
authors: G
authors: G
authors: Boni
authors: E
authors: E
authors: Borsò
authors: A
authors: A
authors: Alsharif
authors: M
authors: M
authors: Grosso
authors: G
authors: G
authors: Manca
authors: C
authors: C
authors: Greco
authors: D
authors: D
authors: Volterrani
authors: G
authors: G
authors: Mariani
mesh_terms: D001859:Bone Neoplasms / Q000150:complications* / Q000188:drug therapy / Q000532:radiotherapy / Q000556:secondary*; D003131:Combined Modality Therapy; D004164:Diphosphonates / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D012968:Etidronic Acid / Q000627:therapeutic use; D006801:Humans; D009942:Organometallic Compounds / Q000627:therapeutic use; D009943:Organophosphorus Compounds / Q000627:therapeutic use; D010146:Pain / Q000188:drug therapy* / Q000209:etiology* / Q000532:radiotherapy; D010166:Palliative Care / Q000379:methods; D018579:Patient Selection; D016499:Radioimmunotherapy; D019275:Radiopharmaceuticals / Q000009:adverse effects / Q000627:therapeutic use*; D013669:Technetium Tc 99m Medronate / Q000031:analogs & derivatives / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D004164:Diphosphonates; D009942:Organometallic Compounds; D009943:Organophosphorus Compounds; D019275:Radiopharmaceuticals; C101598:rhenium-186 HEDP; C024226:technetium Tc 99m hydroxymethylene diphosphonate; C061972:samarium Sm-153 lexidronam; D012968:Etidronic Acid; D013669:Technetium Tc 99m Medronate