To identify the clinical features and independent predictors of survival in patients with bone metastases from prostate cancer （PCa）. We retrospectively analysed 115 PCa patients with bone metastases between 1997 an...To identify the clinical features and independent predictors of survival in patients with bone metastases from prostate cancer （PCa）. We retrospectively analysed 115 PCa patients with bone metastases between 1997 and 2009. The overall survival rate after bone metastases was calculated using the Kaplan-Meier method. The prognostic factors were identified by univariate analysis using a log-rank test and by multivariate analysis using Cox proportional hazards regression models. The follow-up rate was 100%, the follow-up cases during 1, 3 and 5 years were 103, 79 and 55, respectively. The 1-, 3- and 5-year survival rates were 89.1%, 60.9% and 49.8%, respectively, with a median survival time of 48.5 months for patients with bone metastases from PCa. In univariate analysis, age, Gleason score, clinical stage, the number of bone lesions, alkaline phosphatase （ALP） level, invasion of neighbouring organs and non-regional lymph node metastases were correlated with prognosis. By multivariate analysis using Cox regression, ALP level, Gleason score and non-regional lymph node metastases were independent prognostic factors. These prognostic factors will help us to determine the appropriate dose and fraction of radiotherapy for these patients.展开更多
Objective:To summarize the experience of diagnosis and treatment outcomes for bone metastatic prostate cancer.Methods:A retrospective study with a total of 128 prostate cancer(Pca) was performed from 2000 to 2005,in o...Objective:To summarize the experience of diagnosis and treatment outcomes for bone metastatic prostate cancer.Methods:A retrospective study with a total of 128 prostate cancer(Pca) was performed from 2000 to 2005,in our institute.We analyzed the clinical features and outcomes of patients with bone metastases and the data and follow-up of 63 bone metastases was collected by one registrar.Cochran Armitage trend test was used for statistic analysis and a P-value of < 0.05 was taken as statistically significant.Results:The mean age was 73(range 55 to 87) years.The PSA level was from 0.083 ng/mL to 6462 ng/mL.Bone metastases morbidity had good relationship with PSA level.With the mean follow up of 30(range 6 to 72) months for 52/63(82.5%) patients,15(28.8%) died from Pca with a mean survival of 21 months and 1 patient with PSA less than 4 ng/mL at the time died from cerebrovascular suddenness 6 months post-treatment.Conclusion:The early effect of endocrine treatment for bone metastases is obvious,and palliative prostatectomy is satisfactory and able to improve the quality of life rapidly for patients with obstructive symptoms.展开更多
In 2004, docetaxel was approved for the treatment of metastatic castration-resistant prostate cancer （mCRPC）. For the next several years, there was a lull in drug approvals. However, from 2010 onwards, 5 additional ...In 2004, docetaxel was approved for the treatment of metastatic castration-resistant prostate cancer （mCRPC）. For the next several years, there was a lull in drug approvals. However, from 2010 onwards, 5 additional therapies have been approved on the basis of showing a survival benefit in phase III studies. These agents include sipuleuceI-T, cabazitaxel, abiraterone, enzalutamide and （most recently） radium-223. Amongst radiopharmaceuticals currently used for advanced prostate cancer （e.g. samarium-153 and strontium-89）, radium-223 possesses several unique properties. As an alpha-emitting compound, the agent produces a high-energy output over a short range, facilitating selective destruction of tissue within the bone in the region of osteoblastic lesions while sparing surrounding normal tissue. The current review will outline biological rationale for radium-223 and also provide an overview of preclinical and clinical development of the agent. Rational sequencing of radium-223 and combinations, in the increasingly complex landscape of mCRPC will be discussed, along with factors influencing clinical implementation.展开更多
Bone metastases have a major impact on quality of life and survival of patients with advanced prostate cancer,in the last decade,the development and approval of substances inhibiting the vicious cycle of bone metastas...Bone metastases have a major impact on quality of life and survival of patients with advanced prostate cancer,in the last decade,the development and approval of substances inhibiting the vicious cycle of bone metastases have enabled the reduction of complications caused by bone metastases in patients with castration-resistant prostate cancer.These drugs have raised awareness of the importance of skeletal-related events which in the meantime represent an important end point also in trials using agents not specifically designed for bone lesions.Second-generation antihormona]drugs such as enzalutamide or abiraterone have been shown to have a positive impact on the incidence of skeletal complications and therefore provide an important tool in the armamentarium used for treating bone metastases.Radiopharmaceuticals such as radium-223 dichloride([^223Ra])have been demonstrated not only to reduce skeletal-related events and bone-related pain,but also to prolong overall survival,thereby being the first bone-targeting agent showing a survival benefit.As previous studies have not provided an obvious benefit of bone-targeted lesions in castration-sensitive disease,the use of these agents is not recommended.In oligometastatic prostate cancer,the role of local treatment of metastases using stereotactic radiation or radiosurgery is a matter of intense debates and may play an increasing role in the future.展开更多
After being approved by the National Drug Agency in several countries, Radium-223 (Ra-223) is gaining wide acceptance in the treatment of bone metastatic castration resistant prostate cancer. The exact mechanism of ac...After being approved by the National Drug Agency in several countries, Radium-223 (Ra-223) is gaining wide acceptance in the treatment of bone metastatic castration resistant prostate cancer. The exact mechanism of action remain unclear: The established model of direct alpha-particle irradiation from the remodelling bone surface, where Ra-223 accumulates, surrounding the tumor foci can explain a lethal effect only on metastatic microdeposits, but not on higher tumor burden. According to the “pre-metastatic niche model”, it is likely that Ra-223 targets several non-tumoral cell types of the tumor microenvironment involved in the complex mechanism of cancer bone homing and colonization. A deeper insight into this hypothetical mechanism will lead to a more accurate dosimetric approach and to find optimal sequencing and/or combination with the other therapeutic options.展开更多
Objectives: The aim of this study was to describe the diagnostic and etiological aspects of bone metastases in the Rheumatology Department of Cocody’s University Teaching Hospital (UTH). Methodology: This was a descr...Objectives: The aim of this study was to describe the diagnostic and etiological aspects of bone metastases in the Rheumatology Department of Cocody’s University Teaching Hospital (UTH). Methodology: This was a descriptive, 11-year retrospective study (January 1, 2006 to December 31, 2016) of inpatient records of bone metastases. The diagnosis was made on clinical (bone signs), radiological (osteolysis, bone condensation) and sometimes histological basis. Result: Eighty out of 6, 1111 inpatients suffered from bone metastasis with a hospital frequency of 1.30%. The average age was 60.74 years (range 26 to 81 years). Men were predominant (53 men for 27 women) with a sex ratio of 1.96. The main complaints were pain (97.6%). chronic (90%), severe (73.8%), inflammatory (93.8%). There was sometimes a neurological complication: a motor deficit (21.3%), sensitive (13.8%). These symptoms were associated with fever (56.3%) and altered general state (85%). Bone metastases have been revealing in the vast majority of cases (93.75%);the primary cancer was known only in 5 patients (prostate = 2, breast = 2 and cervix = 1). Bone condensation (61.3%), osteolysis (50%) and mixed lesions (7.5%) where the main radiological lesions observed. The primary tumors were: prostatic (50%), pulmonary (18.8%), mammary (11.3%), uterine (5%), renal (2.5%), hepatic (2.5%), bladder (1.3%) and adrenal (1.3%). Conclusion: Bone metastases affect mostly the elderly;inflammatory spinal pain is the main symptom. Bone condensation is the most common radiologic lesion. The prostate, breast and lungs are the main primary tumors.展开更多
Background:Bone metastases are common in patients with advanced cancer.Bisphosphonates(BPs) could prevent or delay the development of skeleton-related events(SREs).The present study aimed to identify the clinical feat...Background:Bone metastases are common in patients with advanced cancer.Bisphosphonates(BPs) could prevent or delay the development of skeleton-related events(SREs).The present study aimed to identify the clinical features of and treatment strategies for Chinese patients with bone metastases.Methods:Consecutive cancer patients who had bone metastases and received BP treatment were enrolled.A questionnaire was developed to collect the patients' clinical data,as well as information on the diagnosis and management of bone metastases.Physicians' awareness of the guidelines and knowledge of the application of BP were also assessed.Results:A total of 3223 patients with lung cancer(36.5%),breast cancer(30.9%),prostate cancer(8.5%),and gastrointestinal cancer(5.7%) were included in this study.The sites of bone metastases were the thoracic spine(56.0%),lumbar spine(47.1%),ribs(32.6%),and pelvis(23.2%).The SRE frequency was the highest in patients with multiple myeloma(36.6%),followed by those with lung cancer(25.9%),breast cancer(20.2%),prostate cancer(18.2%),and gastrointestinal cancer(17.3%).Irradiation to the bone was the most frequent SRE(58%in lung cancer patients,45%in breast cancer patients,and 48%in prostate cancer patients).Our survey also showed that 45.5%of patients received BP within 3 months after their diagnosis of bone metastases,whereas the remaining 54.5%of patients did not receive BP treatment until at least 3 months after their diagnosis of bone metastases.The SRE frequency in the former group was significantly lower than that in the latter group(4.0%vs.42.3%,P < 0.05).In patients with more than 6 months of continuous BP treatment,the mean time to the first SRE was significantly longer than that in patients with less than 6 months of continuous BP treatment(7.2 vs.3.4 months,P < 0.05).In addition,12.2%of the physicians were not aware of the efficacy of BP in preventing and delaying SRE.Only half(52.3%) of the physicians agreed that the BP treatment should persist for at least 6 months unless it was intolerable.Conclusions:Our study suggested that prompt and persistent BP treatment was associated with a reduced risk of SREs.However,our survey also revealed that the proper application of BP was not as common as expected in China.展开更多
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 ...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.展开更多
文摘To identify the clinical features and independent predictors of survival in patients with bone metastases from prostate cancer （PCa）. We retrospectively analysed 115 PCa patients with bone metastases between 1997 and 2009. The overall survival rate after bone metastases was calculated using the Kaplan-Meier method. The prognostic factors were identified by univariate analysis using a log-rank test and by multivariate analysis using Cox proportional hazards regression models. The follow-up rate was 100%, the follow-up cases during 1, 3 and 5 years were 103, 79 and 55, respectively. The 1-, 3- and 5-year survival rates were 89.1%, 60.9% and 49.8%, respectively, with a median survival time of 48.5 months for patients with bone metastases from PCa. In univariate analysis, age, Gleason score, clinical stage, the number of bone lesions, alkaline phosphatase （ALP） level, invasion of neighbouring organs and non-regional lymph node metastases were correlated with prognosis. By multivariate analysis using Cox regression, ALP level, Gleason score and non-regional lymph node metastases were independent prognostic factors. These prognostic factors will help us to determine the appropriate dose and fraction of radiotherapy for these patients.
文摘Objective:To summarize the experience of diagnosis and treatment outcomes for bone metastatic prostate cancer.Methods:A retrospective study with a total of 128 prostate cancer(Pca) was performed from 2000 to 2005,in our institute.We analyzed the clinical features and outcomes of patients with bone metastases and the data and follow-up of 63 bone metastases was collected by one registrar.Cochran Armitage trend test was used for statistic analysis and a P-value of < 0.05 was taken as statistically significant.Results:The mean age was 73(range 55 to 87) years.The PSA level was from 0.083 ng/mL to 6462 ng/mL.Bone metastases morbidity had good relationship with PSA level.With the mean follow up of 30(range 6 to 72) months for 52/63(82.5%) patients,15(28.8%) died from Pca with a mean survival of 21 months and 1 patient with PSA less than 4 ng/mL at the time died from cerebrovascular suddenness 6 months post-treatment.Conclusion:The early effect of endocrine treatment for bone metastases is obvious,and palliative prostatectomy is satisfactory and able to improve the quality of life rapidly for patients with obstructive symptoms.
文摘In 2004, docetaxel was approved for the treatment of metastatic castration-resistant prostate cancer （mCRPC）. For the next several years, there was a lull in drug approvals. However, from 2010 onwards, 5 additional therapies have been approved on the basis of showing a survival benefit in phase III studies. These agents include sipuleuceI-T, cabazitaxel, abiraterone, enzalutamide and （most recently） radium-223. Amongst radiopharmaceuticals currently used for advanced prostate cancer （e.g. samarium-153 and strontium-89）, radium-223 possesses several unique properties. As an alpha-emitting compound, the agent produces a high-energy output over a short range, facilitating selective destruction of tissue within the bone in the region of osteoblastic lesions while sparing surrounding normal tissue. The current review will outline biological rationale for radium-223 and also provide an overview of preclinical and clinical development of the agent. Rational sequencing of radium-223 and combinations, in the increasingly complex landscape of mCRPC will be discussed, along with factors influencing clinical implementation.
文摘Bone metastases have a major impact on quality of life and survival of patients with advanced prostate cancer,in the last decade,the development and approval of substances inhibiting the vicious cycle of bone metastases have enabled the reduction of complications caused by bone metastases in patients with castration-resistant prostate cancer.These drugs have raised awareness of the importance of skeletal-related events which in the meantime represent an important end point also in trials using agents not specifically designed for bone lesions.Second-generation antihormona]drugs such as enzalutamide or abiraterone have been shown to have a positive impact on the incidence of skeletal complications and therefore provide an important tool in the armamentarium used for treating bone metastases.Radiopharmaceuticals such as radium-223 dichloride([^223Ra])have been demonstrated not only to reduce skeletal-related events and bone-related pain,but also to prolong overall survival,thereby being the first bone-targeting agent showing a survival benefit.As previous studies have not provided an obvious benefit of bone-targeted lesions in castration-sensitive disease,the use of these agents is not recommended.In oligometastatic prostate cancer,the role of local treatment of metastases using stereotactic radiation or radiosurgery is a matter of intense debates and may play an increasing role in the future.
文摘After being approved by the National Drug Agency in several countries, Radium-223 (Ra-223) is gaining wide acceptance in the treatment of bone metastatic castration resistant prostate cancer. The exact mechanism of action remain unclear: The established model of direct alpha-particle irradiation from the remodelling bone surface, where Ra-223 accumulates, surrounding the tumor foci can explain a lethal effect only on metastatic microdeposits, but not on higher tumor burden. According to the “pre-metastatic niche model”, it is likely that Ra-223 targets several non-tumoral cell types of the tumor microenvironment involved in the complex mechanism of cancer bone homing and colonization. A deeper insight into this hypothetical mechanism will lead to a more accurate dosimetric approach and to find optimal sequencing and/or combination with the other therapeutic options.
文摘Objectives: The aim of this study was to describe the diagnostic and etiological aspects of bone metastases in the Rheumatology Department of Cocody’s University Teaching Hospital (UTH). Methodology: This was a descriptive, 11-year retrospective study (January 1, 2006 to December 31, 2016) of inpatient records of bone metastases. The diagnosis was made on clinical (bone signs), radiological (osteolysis, bone condensation) and sometimes histological basis. Result: Eighty out of 6, 1111 inpatients suffered from bone metastasis with a hospital frequency of 1.30%. The average age was 60.74 years (range 26 to 81 years). Men were predominant (53 men for 27 women) with a sex ratio of 1.96. The main complaints were pain (97.6%). chronic (90%), severe (73.8%), inflammatory (93.8%). There was sometimes a neurological complication: a motor deficit (21.3%), sensitive (13.8%). These symptoms were associated with fever (56.3%) and altered general state (85%). Bone metastases have been revealing in the vast majority of cases (93.75%);the primary cancer was known only in 5 patients (prostate = 2, breast = 2 and cervix = 1). Bone condensation (61.3%), osteolysis (50%) and mixed lesions (7.5%) where the main radiological lesions observed. The primary tumors were: prostatic (50%), pulmonary (18.8%), mammary (11.3%), uterine (5%), renal (2.5%), hepatic (2.5%), bladder (1.3%) and adrenal (1.3%). Conclusion: Bone metastases affect mostly the elderly;inflammatory spinal pain is the main symptom. Bone condensation is the most common radiologic lesion. The prostate, breast and lungs are the main primary tumors.
文摘Background:Bone metastases are common in patients with advanced cancer.Bisphosphonates(BPs) could prevent or delay the development of skeleton-related events(SREs).The present study aimed to identify the clinical features of and treatment strategies for Chinese patients with bone metastases.Methods:Consecutive cancer patients who had bone metastases and received BP treatment were enrolled.A questionnaire was developed to collect the patients' clinical data,as well as information on the diagnosis and management of bone metastases.Physicians' awareness of the guidelines and knowledge of the application of BP were also assessed.Results:A total of 3223 patients with lung cancer(36.5%),breast cancer(30.9%),prostate cancer(8.5%),and gastrointestinal cancer(5.7%) were included in this study.The sites of bone metastases were the thoracic spine(56.0%),lumbar spine(47.1%),ribs(32.6%),and pelvis(23.2%).The SRE frequency was the highest in patients with multiple myeloma(36.6%),followed by those with lung cancer(25.9%),breast cancer(20.2%),prostate cancer(18.2%),and gastrointestinal cancer(17.3%).Irradiation to the bone was the most frequent SRE(58%in lung cancer patients,45%in breast cancer patients,and 48%in prostate cancer patients).Our survey also showed that 45.5%of patients received BP within 3 months after their diagnosis of bone metastases,whereas the remaining 54.5%of patients did not receive BP treatment until at least 3 months after their diagnosis of bone metastases.The SRE frequency in the former group was significantly lower than that in the latter group(4.0%vs.42.3%,P < 0.05).In patients with more than 6 months of continuous BP treatment,the mean time to the first SRE was significantly longer than that in patients with less than 6 months of continuous BP treatment(7.2 vs.3.4 months,P < 0.05).In addition,12.2%of the physicians were not aware of the efficacy of BP in preventing and delaying SRE.Only half(52.3%) of the physicians agreed that the BP treatment should persist for at least 6 months unless it was intolerable.Conclusions:Our study suggested that prompt and persistent BP treatment was associated with a reduced risk of SREs.However,our survey also revealed that the proper application of BP was not as common as expected in China.
文摘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.
