Strontium-89 (Sr-89) is a pure emitter with maximum beta energy of 1.46 MeV, average beta energy of 0.58 MeV, and a physical half-life of 50.5 days. It is rapidly taken up by bone and preferentially retained at the sites of osseous metastases. Its biological half-life is >50 days at the metastatic sites, but about 14 days only in the normal bone. The dose of its absorption in the tumor-bearing bone ranges from 21 +/- 4 to 231 +/- 56 cGy/MBq, 2-25 times higher than in the normal bone. Strontium-89 therapy is an effective palliative treatment of bone metastases from prostate cancer, with analgesic effectiveness in 80%.
Bone Neoplasms ; radiotherapy ; secondary ; Humans ; Male ; Neoplasm Metastasis ; Prostatic Neoplasms ; pathology ; radiotherapy ; Strontium Radioisotopes ; therapeutic use

OBJECTIVETo investigate the influence of (89)SrCl(2) (strontium-89 chloride) on immune functions in patients with simple bone metastases.

METHODSTwenty-five patients diagnosed as simple bone metastases with un-detectable primary tumors were treated with (89)SrCl(2). The CD4(+), CD8(+), CD4(+)/CD8(+) lymphocyte subsets were assessed before and after (89)SrCl(2) treatment. Twenty normal individuals served as controls.

RESULTSThe CD4(+), CD8(+) and CD4(+)/CD8(+) in the control group were (38.83 +/- 8.95)%, (32.19 +/- 8.51)% and 1.29 +/- 0.47, respectively. In patients, they were (31.12 +/- 8.12)%, (41.75 +/- 10.91)% and 0.84 +/- 0.22 before treatment, and (36.21 +/- 8.71)%, (35.08 +/- 10.14)% and 1.19 +/- 0.27 after treatment, respectively (P < 0.05). The patients were divided into treatment effective and non-effective groups by pain score. Before treatment, the immunologic parameters in the two groups had no significant differences (P > 0.05). After treatment, the frequencies of CD4(+) and CD8(+) subsets, CD4(+) to CD8(+) ratios and the number of metastatic foci in the effective group were (37.81 +/- 5.18)%, (33.17 +/- 6.38)%, 1.33 +/- 0.31 and 6.64 +/- 3.11, respectively, while in the treatment non-effective group, they were (32.09 +/- 5.72)%, (39.99 +/- 5.38)%, 0.82 +/- 0.22 and 9.87 +/- 3.46, respectively (P < 0.05).

CONCLUSIONThe immune functions in patients with simple bone metastases are inhibited. Treatment with (89)SrCl(2) may improve their immunity to certain extent. The degree of recovery in the treatment effective patients was better than that in the treatment non-effective cases.

Adult ; Aged ; Bone Neoplasms ; immunology ; radiotherapy ; secondary ; CD4-CD8 Ratio ; Female ; Humans ; Male ; Middle Aged ; Neoplasms, Unknown Primary ; immunology ; radiotherapy ; Strontium ; therapeutic use ; Strontium Radioisotopes ; therapeutic use ; T-Lymphocyte Subsets ; immunology

Bone metastases are the main driver of morbidity and mortality in advanced prostate cancer. Targeting the bone microenvironment, a key player in the pathogenesis of bone metastasis, has become one of the mainstays of therapy in men with advanced prostate cancer. This review will evaluate the data supporting the use of bone-targeted therapy, including (1) bisphosphonates such as zoledronic acid, which directly target osteoclasts, (2) denosumab, a receptor activator of nuclear factor-kappa B (RANK) ligand inhibitor, which targets a key component of bone stromal interaction, and (3) radium-223, an alpha-emitting calcium mimetic, which hones to the metabolically active areas of osteoblastic metastasis and induces double-strand breaks in the DNA. Denosumab has shown enhanced delay in skeletal-related events compared to zoledronic acid in patients with metastatic castration-resistant prostate cancer (mCRPC). Data are mixed with regard to pain control as a primary measure of efficacy. New data call into question dosing frequency, with quarterly dosing strategy potentially achieving similar effect compared to monthly dosing for zoledronic acid. In the case of radium-223, there are data for both pain palliation and improved overall survival in mCRPC. Further studies are needed to optimize timing and combination strategies for bone-targeted therapies. Ongoing studies will explore the impact of combining bone-targeted therapy with investigational therapeutic agents such as immunotherapy, for advanced prostate cancer. Future studies should strive to develop biomarkers of response, in order to improve efficacy and cost-effectiveness of these agents.
Bone Density Conservation Agents/therapeutic use* ; Bone Neoplasms/secondary* ; Denosumab/therapeutic use* ; Diphosphonates/therapeutic use* ; Endothelins/antagonists & inhibitors* ; Humans ; Male ; Prostatic Neoplasms/pathology* ; Protein Kinase Inhibitors/therapeutic use* ; Radioisotopes/therapeutic use* ; Radiopharmaceuticals/therapeutic use* ; Radium/therapeutic use* ; Samarium/therapeutic use* ; Strontium Radioisotopes/therapeutic use*

Bone metastases are a major problem in the clinical management of patients with prostate cancer. Despite the use of analgesic for the relief of such pain, the outcomes are not often satisfactory. Strontium-89 (89Sr) is a pure beta-emitting radioisotope to be avidly concentrated in the areas of high osteoblastic activity. The aim of this study was to evaluate the efficacy of 89Sr in the therapy for bone metastases of prostate carcinoma. 116 patients received intravenous injection of 89Sr at the dose of 3mCi (111MBq). All patients underwent physical examination and Karnofsky's Performance Score (KPS) evaluation before and after administration; the analgesic effects were evaluated by scores of pain. The complete response (CR) was defined as scores of pain > 75%; no response (NR) was defined as scores of pain < 25% the remaining was partial response (PR). The changes of bone metastases were screened by CT, MRI and 99mTc-MDP bone scintigraphy according to the standards of WHO. After the treatment with 89Sr, the total response rate was 80.2%. In the 116 cases, 21 cases (18.1%) displayed complete response and 72 cases (62.1%) displayed partial response, but 23 cases (19.2%) showed no response. The mean score on Karnfsky's performance status (KPS) was 20.0% higher. About 1/3 cases exhibited an obvious decrease in the number of metastases, and some foci disappeared. Thirteen cases (12%) showed a greater decrease in prostate-specific antigen (PSA) value. 89Sr chloride is an effective and safe therapy of the bone metastases from prostate cancer.
Adult ; Aged ; Aged, 80 and over ; Bone Neoplasms ; radiotherapy ; secondary ; Humans ; Male ; Middle Aged ; Prostatic Neoplasms ; pathology ; radiotherapy ; Strontium Radioisotopes ; therapeutic use

OBJECTIVETo evaluate the efficacy of strontium-89 (89Sr) in the treatment of painful bone metastases of prostate cancer.

METHODSA total of 116 patients with painful bone metastases of prostate cancer received bilateral orchiectomy and incretion, followed by intravenous injection of 89Sr at the dose of 1.48-2.22 MBq (40-60 microCi)/kg. The clinical effects were evaluated by follow-up analysis.

RESULTSAfter the 89Sr treatment, appetite and sleep were evidently improved in 33.6% and 56.0% of the patients respectively, the applied dose of anodyne reduced in 61.2%, pain alleviated in 83.6%, with an absolute palliation rate of 24.1%. Pain relief started at 3-21 (10.2 +/- 6.5) days and lasted 3-12 (5.3 +/- 2.2) months. Flare ache occurred in 31.9% of the patients. Compared with pre-treatment, the mean score on Karnofsky's performance status (KPS) was 20.0% higher, and the WBC count decreased to 3.0-3.9 x 10(6)/L in 18.1% of the patients. Whole body bone scintigraphy of 53 followed-up patients showed that 39 (73.6%) of them exhibited an obvious decrease in the number of metastases, 10 (18.9% remained in a stabilized state and only 4 (7.5% deteriorated.

CONCLUSION89Sr, capable of inhibiting bone metastasis, palliating pain and improving the quality of life with few adverse effects, can be used as a desirable therapeutic for painful bone metastases of prostate cancer.

Aged ; Aged, 80 and over ; Bone Neoplasms ; radiotherapy ; secondary ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Pain, Intractable ; radiotherapy ; Prostatic Neoplasms ; pathology ; Strontium Radioisotopes ; therapeutic use ; Treatment Outcome

OBJECTIVETo compare the clinical curative effects between 89Sr and its combination with the Guliu recipe (GLR, a Chinese herbal medicine) in treating multiple bone metastatic tumor of mammary cancer (MBM-MC).

METHODSBy adopting the random sampling and grouping method, 89Sr alone (Sr) and 89Sr combined with CHM (Sr-GLR) were used in treating 86 and 40 patients with MBM-MC respectively. The efficacy of therapy were appraised according to the degree of ostalgia relieving and quality of life (QOF) in patients, and the effect of treatment on focal bone metabolism and bone marrow hematopoietic function were compared.

RESULTSThe effective rate of Sr and Sr-GLR in relieving ostalgia was 83.72% and 95.00%, respectively (P > 0.05), the QOF improving and stabilizing rate of them 80.23% and 95.00% (P < 0.05), the effective rate on focal bone metabolism 59.30% and 52.50% (P > 0.05) and their hemo-toxicity 28.00% and 30.00% (P > 0.05).

CONCLUSIONSr-GLR is a combination therapy in treating MBM-MC with good effect, it could raise the patient's QOF, enhance the ostalgia relieving effect without increasing the hemo-toxicity of treatment.

Adult ; Aged ; Bone Neoplasms ; drug therapy ; radiotherapy ; secondary ; Breast Neoplasms ; drug therapy ; pathology ; radiotherapy ; Carcinoma, Ductal, Breast ; drug therapy ; radiotherapy ; secondary ; Combined Modality Therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Middle Aged ; Phytotherapy ; Quality of Life ; Strontium Radioisotopes ; therapeutic use

OBJECTIVETo analyze the potential mechanism of preventive and therapeutic effects of (90)Sr on hypertrophic scar, and to observe its clinical effect.

METHODSFibroblasts isolated from human hypertrophic scar were cultured in vitro and radiated by (90)Sr with the dose varying from 0 Gy (control group) to 5 Gy (LD group), 10 Gy (MD group), and 15 Gy (HD group). The cell cycle and apoptosis rate were determined by flow cytometry at post radiation hour (PRH) 24, 48, and 72. The concentration of type I collagen in cell supernatant was detected by enzyme-linked immunosorbent assay (ELISA). Therapeutic effects of (90)Sr radiation were evaluated among 348 patients with hypertrophic scars, 40 patients with keloids, and 114 patients for scar prevention after surgical operation. The number of fibroblasts after HE staining was compared among normal skin tissue, hypertrophic scar, and hypertrophic scar treated with (90)Sr radiation. Data were processed with one-way analysis of variance and q test.

RESULTS(1) Apoptotic rates in MD and HD groups at PRH 48 were higher than those at PRH 24, and the apoptotic rate was similar between MD group and HD group at PRH 72. Apoptotic rate in LD group at PRH 48 was significantly higher than that at PRH 24, but it decreased rapidly at PRH 72, which was significantly lower than those in MD and HD groups (with F values all equal to 916.711, P values all below 0.01). (2) At PRH 24, cell ratios of each phase in LD and HD groups were similar, and cell ratio of S phase in HD group [(48.1 ± 1.0)%] was higher than those in the other three groups (with F values all equal to 200.277, P values all below 0.01). At PRH 72, cell ratio of S phase in MD and HD groups was respectively (85.7 ± 5.2)%, (73.0 ± 8.4)%, implying that cells were blocked in S phase, and the values were all higher than those in control and LD groups (with F values all equal to 111.105, P values all below 0.01). (3) At the same time point, the concentration of type I collagen decreased along with the increase of radiation dose (with F values from 5044.449 to 8234.432, P values all below 0.01). With the same radiation dose, the concentration of type I collagen increased along with prolongation of time (with F values from 333.395 to 2973.730, P values all below 0.01). (4) Clinical observation showed the (obvious) effective rate of radiation for pathological scars and that for scar prevention after surgical operation added up to 88.45%. The number of fibroblasts per 200 times visual field in patients after (90)Sr radiation (86 ± 20) was less than that in patients without treatment [(198 ± 65), F = 208.405, P < 0.05].

CONCLUSIONSThe effect of (90)Sr radiation on fibroblasts and extracellular matrix can contribute to inhibition of scar formation, and the clinical effect is significant.

Adolescent ; Adult ; Apoptosis ; radiation effects ; Cell Cycle ; radiation effects ; Cells, Cultured ; Child ; Child, Preschool ; Cicatrix, Hypertrophic ; metabolism ; pathology ; radiotherapy ; Collagen Type I ; metabolism ; Female ; Fibroblasts ; radiation effects ; Humans ; Male ; Strontium Radioisotopes ; therapeutic use ; Young Adult

OBJECTIVETo evaluate the clinical value of (89)SrCl(2) (Ke xing Inc, Shanghai) as a palliative therapy modality for cancer patients with bone metastasis.

METHODSIn 504 cancer patients with painful limitation of movement due to bony metastasis, a dose of 1.48-2.22 MBq/kg (40-60 uCi/kg) iv infusion of (89)SrCl(2) was given.

RESULTSIn 97 patients (19.2%) there was no improvement in pain and life quality, 298 patients (59.1%) showed mild to moderate improvement (moderately effective), 109 patients (21.6%) became free of pain and were subsequently fully ambulatory (markedly effective). The pain relief appeared from D1-D46 after (89)SrCl(2) administration, most frequently from D5-D14. The palliative effect could last for about 56 days to 13 months. Repeated bone scans of some patients showed that the metastatic foci in the bone became smaller or even disappeared gradually after the administration of (89)SrCl(2). Approximately 55% of patients experienced grade I approximately III bone marrow depression attributable to (89)SrCl(2), which would return to the pre-treatment level within 3 approximately 9 months.

CONCLUSION(89)SrCl(2) is effective and safe for the relief of bone pain and improvement of quality of life in cancer patients with painful bony metastasis.

Adult ; Aged ; Aged, 80 and over ; Bone Neoplasms ; complications ; radiotherapy ; secondary ; Breast Neoplasms ; pathology ; Female ; Humans ; Lung Neoplasms ; pathology ; Male ; Middle Aged ; Pain Measurement ; Pain, Intractable ; etiology ; radiotherapy ; Quality of Life ; Strontium Radioisotopes ; therapeutic use

OBJECTIVETo evaluate the safety and efficacy of strontium-89-chloride for management of bone metastases in patients without bone pain.

METHODSFifty-four patients without painful bone metastases were given a single intravenous dose (1.48-2.22 MBq/kg) of strontium-89-chloride, which was repeated once or twice at the interval between 3 and 6 months.

RESULTSThe total response rate was 74.0% in these, and the response rate was significantly lower in patients with focal size>2 cm than in those with focal sizestrontium-89-chloride included mainly thrombocytopenia and neutropenia, mostly mild and reversible without interventions.

CONCLUSIONStrontium-89-chloride is effective and safe for treatment of nonpainful bone metastases.

Adult ; Aged ; Aged, 80 and over ; Bone Neoplasms ; complications ; radiotherapy ; secondary ; Female ; Humans ; Lung Neoplasms ; pathology ; Male ; Middle Aged ; Pain ; etiology ; Prostatic Neoplasms ; pathology ; Strontium Radioisotopes ; therapeutic use ; Treatment Outcome

AIMTo investigate the transforming growth factor beta1 (TGF-beta1) and basic fibroblast growth factor (bFGF) expressions in benign prostatic hyperplasia (BPH) and the effect of beta-radiation.

METHODSTGF-beta1 and bFGF expression was studied by means of an immunohistochemical method in nine normal prostatic (NP) tissues, 15 hyperplastic prostatic tissues and 35 hyperplastic prostatic tissues treated with 90Sr/90Y.

RESULTSThe TGF-beta1 expression in the epithelium and stroma of normal prostatic tissues was 68.2 % +/- 10.5 % and 29.7 % +/- 4.6 %, respectively, while it was 64.8 % +/- 9.3 % and 28.6 % +/- 4.1 %, respectively, in hyperplastic prostatic tissues. Compared with the controls, TGF-beta1 expression in the epithelia and stroma of BPH treated with 90Sr/90Y increased significantly (P <0.01). The bFGF expression in epithelia and stroma of normal prostatic tissues was 17.4 % +/- 3.7 % and 42.5 % +/- 6.8 %, respectively, and was 46.3 % +/- 8.2 % and 73.2 % +/- 12.1 %, respectively, in hyperplastic prostatic tissues. Compared with the controls, expressions of bFGF in the epithelia and stroma of BPH treated with a 90Sr/90Y prostatic hyperplasia applicator decreased significantly (P <0.01).

CONCLUSIONExposure of beta-rays had noticeable effects on BPH tissues, enhancing TGF-beta1 expression and inhibiting bFGF expression.

Aged ; Aged, 80 and over ; Beta Particles ; Case-Control Studies ; Fibroblast Growth Factor 2 ; metabolism ; radiation effects ; Gene Expression ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Prostate ; metabolism ; radiation effects ; Prostatic Hyperplasia ; metabolism ; radiotherapy ; Strontium Radioisotopes ; therapeutic use ; Transforming Growth Factor beta ; metabolism ; radiation effects ; Transforming Growth Factor beta1 ; Yttrium Radioisotopes ; therapeutic use