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Sample records for cancer bone metastases

  1. Ca2 Receptor, Prostate Cancer, and Bone Metastases

    National Research Council Canada - National Science Library

    Brown, Edward M

    2006-01-01

    14. ABSTRACT While bony metastases of prostate cancer are often osteoblastic, excessive bone resorption also occurs in the sites of metastases, which contributes to skeletal complications (e.g., pain, fractures...

  2. Ca2+ Receptor, Prostate Cancer, and Bone Metastases

    National Research Council Canada - National Science Library

    Brown, Edward M

    2005-01-01

    While bony metastases of prostate cancer are often osteoblastic, excessive bone resorption also occurs in the sites of metastases, which contributes to skeletal complications (e.g., pain, fractures...

  3. Unexpected Bone Metastases from Thyroid Cancer

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    Sandra Gibiezaite

    2015-01-01

    Full Text Available Objective. To present a complicated case of differentiated thyroid carcinoma (DTC with metastases to the skull that was evident on I-131 whole body scan (WBS but negative on other imaging modalities in a low risk patient. Methods. We will discuss clinical course, imaging, pathological findings, and treatment of the patient with skull metastasis from DTC. Pertinent literature on imaging and pathology findings as well as radioactive iodine (RAI treatment impact on quality of life and survival in patients with bone metastases from DTC will be reviewed. Results. The patient is a 37-year-old woman with a diagnosis of DTC who had focal areas of increased uptake in the head on WBS with no correlative findings on CT and MRI. Initially, false positive findings were suspected since patient had a low risk for developing metastases. However, the persistent findings on post-RAI treatment WBS, following two courses of treatment, were highly concerning for metastatic bone disease. WBC performed 6 months following the second RAI treatment revealed resolution of the findings. Conclusions. False positive findings in WBS are frequent and may be due to contamination, perspiration, or folliculitis of the scalp as well as benign lesions such as meningioma, hematoma, cavernous angioma, and metallic sutures. However, metastatic disease should always be considered even if the patient has low risk of distant metastatic disease and correlative images do not support the diagnosis. RAI therapy appears to improve the survival rates and quality of life of thyroid cancer patients with bone metastases based on retrospective studies.

  4. The Breast Cancer to Bone (B2B) Metastases Research Program: a multi-disciplinary investigation of bone metastases from breast cancer

    National Research Council Canada - National Science Library

    Brockton, Nigel T; Gill, Stephanie J; Laborge, Stephanie L; Paterson, Alexander H G; Cook, Linda S; Vogel, Hans J; Shemanko, Carrie S; Hanley, David A; Magliocco, Anthony M; Friedenreich, Christine M

    2015-01-01

    .... The Breast Cancer to Bone (B2B) Metastases Research Program consists of a prospective cohort of incident breast cancer patients and four sub-projects that are investigating priority areas in breast cancer bone metastases...

  5. SURGICAL TREATMENT FOR BONE METASTASES OF KIDNEY CANCER

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    A. S. Semkov

    2010-01-01

    Full Text Available The data of 67 kidney cancer (KC patients with bone metastases, who had been treated at Moscow City Cancer Hospital Sixty-Two in 2002 to 2009 and had undergone skeletal bone surgery, were retrospectively analyzed. The role of surgical treatment for bone metastases from KC was assessed and the factors influencing the patients survival were determined. Surgical treatment for bone metastases from KC was ascertained to yield satisfactory results in improving the quality of life and increasing survival rates in the patients.

  6. SURGICAL TREATMENT FOR BONE METASTASES OF KIDNEY CANCER

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    A. S. Semkov

    2014-08-01

    Full Text Available The data of 67 kidney cancer (KC patients with bone metastases, who had been treated at Moscow City Cancer Hospital Sixty-Two in 2002 to 2009 and had undergone skeletal bone surgery, were retrospectively analyzed. The role of surgical treatment for bone metastases from KC was assessed and the factors influencing the patients survival were determined. Surgical treatment for bone metastases from KC was ascertained to yield satisfactory results in improving the quality of life and increasing survival rates in the patients.

  7. Prevention and Treatment of Bone Metastases in Breast Cancer

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    Ripamonti Carla

    2013-09-01

    Full Text Available In breast cancer patients, bone is the most common site of metastases. Medical therapies are the basic therapy to prevent distant metastases and recurrence and to cure them. Radiotherapy has a primary role in pain relief, recalcification and stabilization of the bone, as well as the reduction of the risk of complications (e.g., bone fractures, spinal cord compression. Bisphosphonates, as potent inhibitors of osteoclastic-mediated bone resorption are a well-established, standard-of-care treatment option to reduce the frequency, severity and time of onset of the skeletal related events in breast cancer patients with bone metastases. Moreover bisphosphonates prevent cancer treatment-induced bone loss. Recent data shows the anti-tumor activity of bisphosphonates, in particular, in postmenopausal women and in older premenopausal women with hormone-sensitive disease treated with ovarian suppression. Pain is the most frequent symptom reported in patients with bone metastases, and its prevention and treatment must be considered at any stage of the disease. The prevention and treatment of bone metastases in breast cancer must consider an integrated multidisciplinary approach.

  8. Radium-223 Therapy of Bone Metastases in Prostate Cancer.

    Science.gov (United States)

    Nilsson, Sten

    2016-11-01

    Metastatic castration-resistant prostate cancer frequently metastasizes to the bone, often resulting in painful skeletal events, reduced quality of life, and reduced survival. Radium-223 is a first-in-class alpha-emitting radiopharmaceutical that has proven to prolong overall survival, delay time to symptomatic skeletal events, and improve quality of life in patients with castration-resistant prostate cancer and symptomatic bone metastases and no visceral metastases. Radium-223 provides survival benefit to patients with castration-resistant prostate cancer and symptomatic bone metastases, regardless of prior docetaxel use. This article gives an overview of the development of radium-223 from the first-in-human trial to current status. Copyright © 2016. Published by Elsevier Inc.

  9. Urothelial Cancer With Occult Bone Marrow Metastases and Isolated Thrombocytopenia

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    Ajjai Alva

    2015-07-01

    Full Text Available Bladder cancer rarely presents clinically with a myelophthisic picture from diffuse bone marrow infiltration especially in the absence of detectable skeletal metastases. A 75-year old man presented with newly diagnosed urothelial cell carcinoma of the bladder. Pathology from transurethral resection of bladder tumor demonstrated muscle-invasive disease. Pre-therapy imaging including CT abdomen/pelvis, CXR and bone scan demonstrated liver lesions concerning for metastatic disease but no skeletal metastases. Labs were notable for isolated thrombocytopenia, hypercalcemia and acute kidney injury prompting hospitalization. Hematologic work-up including bone marrow aspiration and biopsy revealed diffuse infiltration of the bone marrow by urothelial cancer. The case illustrates the importance of fully investigating otherwise unexplained clinical findings in patients with clinically localized urothelial cancer prior to curative intent surgery.

  10. Urothelial Cancer With Occult Bone Marrow Metastases and Isolated Thrombocytopenia.

    Science.gov (United States)

    Alva, Ajjai; Davis, Elizabeth; Chinnaiyan, Arul M; Dhanasekaran, Saravana; Mehra, Rohit

    2015-07-01

    Bladder cancer rarely presents clinically with a myelophthisic picture from diffuse bone marrow infiltration especially in the absence of detectable skeletal metastases. A 75-year old man presented with newly diagnosed urothelial cell carcinoma of the bladder. Pathology from transurethral resection of bladder tumor demonstrated muscle-invasive disease. Pre-therapy imaging including CT abdomen/pelvis, CXR and bone scan demonstrated liver lesions concerning for metastatic disease but no skeletal metastases. Labs were notable for isolated thrombocytopenia, hypercalcemia and acute kidney injury prompting hospitalization. Hematologic work-up including bone marrow aspiration and biopsy revealed diffuse infiltration of the bone marrow by urothelial cancer. The case illustrates the importance of fully investigating otherwise unexplained clinical findings in patients with clinically localized urothelial cancer prior to curative intent surgery.

  11. SURGICAL TREATMENT FOR KIDNEY CANCER METASTASES TO THE LONG TUBULAR BONES

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    S. V. Kostritsky

    2014-07-01

    Full Text Available The data of 35 kidney cancer patients with metastases in long bones, who had been operated, were retrospectively analyzed. The role of surgery in patients with long bones metastases of kidney cancer was assessed and application of surgical treatment was ascertained to yield satisfactory results in improving the quality of life and duration of life in patients with solitary bone metastases.

  12. SURGICAL TREATMENT FOR KIDNEY CANCER METASTASES TO THE LONG TUBULAR BONES

    Directory of Open Access Journals (Sweden)

    S. V. Kostritsky

    2013-01-01

    Full Text Available The data of 35 kidney cancer patients with metastases in long bones, who had been operated, were retrospectively analyzed. The role of surgery in patients with long bones metastases of kidney cancer was assessed and application of surgical treatment was ascertained to yield satisfactory results in improving the quality of life and duration of life in patients with solitary bone metastases.

  13. Treatment with bone-seeking radionuclides for painful bone metastases in patients with lung cancer

    DEFF Research Database (Denmark)

    Zacho, Helle D; Karthigaseu, Nita Nishanthiny; Fuglsang, Randi

    2017-01-01

    Treatment with bone-seeking radionuclides may provide palliation from pain originating from bone metastases. However, most studies have been conducted in patients with prostate cancer and patients with breast cancer. We aimed to perform a systematic review of the use of radionuclide treatment in ...

  14. Prevention of Bone Metastases in Breast Cancer Patients. Therapeutic Perspectives

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    Philippe Beuzeboc

    2014-05-01

    Full Text Available One in four breast cancer patients is at risk of developing bone metastases in her life time. The early prevention of bone metastases is a crucial challenge. It has been suggested that the use of zoledronic acid (ZOL in the adjuvant setting may reduce the persistence of disseminated tumor cells and thereby might improve outcome, specifically in a population of patients with a low estrogen microenvironment. More recently, the results of a large meta-analysis from 41 randomized trials comparing a bisphosphonate (BP to placebo or to an open control have been presented at the 2013 San Antonio Breast Cancer Meeting. Data on 17,016 patients confirm that adjuvant BPs, irrespective of the type of treatment or the treatment schedule and formulation (oral or intra-venously (IV, significantly reduced bone recurrences and improved breast cancer survival in postmenopausal women. No advantage was seen in premenopausal women. BPs are soon likely to become integrated into standard practice. Published data on the mechanisms involved in tumor cell seeding from the primary site, in homing to bone tissues and in the reactivation of dormant tumor cells will be reviewed; these might offer new ideas for innovative combination strategies.

  15. Wnt Signaling in Prostate Cancer Bone Metastases

    Science.gov (United States)

    2016-11-01

    Pten, Estrous Cycle MCB - 11 THE EFFECT OF HDACI (AR-42) ON CANINE PROSTATE CANCER METASTASIS. S. Elshafae1, N. Kohart1, L... canine prostate cancer overexpressing Dkk-1 was used in this study to investigate how enhanced Wnt/JNK signaling could alter tumor growth, metastasis and...metastatic phenotype of prostate cancer. Ace-1-Dkk-1, a canine prostate cancer overexpressing human Dkk-1, previously developed in our lab was used in

  16. Risk factors and characteristics of prostate cancer bone metastases

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    Jun-ming LIN

    2017-10-01

    Full Text Available Objective To analyze the risk factors and characteristics of bone metastases in patients with prostate cancer. Methods Patients who were diagnosed as prostate cancer by biopsy and histopathologic analysis between June 2006 and June 2016 were included in this study. The clinical data of the patients were reviewed, and the demographic data, laboratory examination results and Gleason score were recorded. The correlations between clinical factors and bone metastasis were analyzed, and the risk factors of bone metastasis were identified. Results A total of 585 patients were recruited in this study, including 228 with bone metastasis and 357 without bone metastasis. Of the patients with bone metastasis, the incidence of pelvic metastasis was the highest, accounting for 81.58%, followed by spin (63.16% and rib (58.33%, and the incidence of clavicle metastasis was the lowest (14.47%. Logistic regression analysis showed that age 85.5U/L, prostate-specific antigen >79.88μg/L and Gleason score >7.5 were the risk factors of bone metastasis in prostate cancer. ROC curve analysis showed that the sensitivity of diagnosing bone metastasis was 56.1%, 66.7%, 68.4% and 56.1%, and the specificity was 56.6%, 81.8%, 70.0% and 65.3%, respectively for above 4 factors. Conclusions The most common site of bone metastasis in patients with prostate cancer is pelvis. Patients' age, concentrations of plasma ALP and PSA, and Gleason score are the risk factors for bone metastasis in patients with prostate cancer. DOI: 10.11855/j.issn.0577-7402.2017.08.09

  17. Clinical characteristics and risk factors for developing bone metastases in patients with breast cancer

    OpenAIRE

    Chen, Wen-Zhao; Shen, Jun-Feng; Zhou, Yang; Xuan-yin CHEN; Liu, Jia-Ming; Liu, Zhi-Li

    2017-01-01

    The risk factors for predicting bone metastases in patients with breast cancer are still controversial. Here, a total of 2133 patients with breast cancer, including 327 with bone metastases (15.33%) and 1806 without bone metastases (84.67%) were retrospective reviewed from January 2005 to December 2015. The spine was found to be the most common site for bone metastases, followed by ribs (57.5%), pelvis (54.1%) and sternum (44.3%). The results indicated that axillary lymph node metastases and ...

  18. [Predictive factors for bone metastases of prostate cancer].

    Science.gov (United States)

    Chen, Ye-Hui; Nie, Pin; Jiang, Wen; Zhao, Shi-Jia; Zhang, Zhi; Lin, Hua-Xin; Li, Miao-Yuan; Liu, Yan-Qing; Li, Peng-Hui; Zhu, Xu-Sheng

    2016-02-01

    To investigate the correlation between a diverse of clinical factors and bone metastases of prostate cancer. The clinical data of 80 patients with prostate cancer were collected and analyzed. The correlations of age, alkaline phosphotase (ALP), prostate specific antigen (PSA), erythrocyte sedimentation rate (ESR), Gleason score, and expressions of androgen receptor (AR) and Ki-67 with bone metastases were analyzed by one-way ANOVA and Logistic regression analysis. The cutoff value, sensitivity and specificity of the independent correlation factors were calculated. Forty-five of the 80 patients (56%) were found to have bone metastasis, who had significantly older age and higher levels of ALP, PSA, ESR, Gleason score, and expressions of AR and Ki-67 than those without bone metastasis (PGleason score and AR expression as independent factors correlated with bone metastasis with OR (95% CI) of 1.005 (1.001, 1.009) (P=0.008), 5.356 (1.431, 20.039) (P=0.013), and 18.594 (2.460, 140.524) (P=0.005), respectively. The cutoff values of PSA, Gleason Score and AR were 67.1 ng/ml, 7.5, and 2.5, respectively; their sensitivities were 55.6%, 75.6%, and 84.0% for predicting bone metastasis with specificities of 97.1%, 82.9%, and 91.4%, respectively. Of the factors analyzed, PSA, Gleason score and AR expression, but not age, ALP, PSA, ESR, or Ki-67 expression, are the predictive factors of bone metastasis of prostate cancer.

  19. Bone-Targeted Agents for the Management of Breast Cancer Patients with Bone Metastases

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    Demetrios Simos

    2013-08-01

    Full Text Available Despite advances in adjuvant therapy for breast cancer, bone remains the most common site of recurrence. The goal of therapy for these patients is palliative and focused on maximizing the duration and quality of their life, while concurrently minimizing any disease or treatment-related complications. Bone metastases predispose patients to reduced survival, pain, impaired quality of life and the development of skeletal-related events. With an increased understanding of the pathophysiology of bone metastasis, effective treatments for their management have evolved and are now in widespread clinical use. This article will discuss the pathogenesis of bone metastases and review the key clinical evidence for the efficacy and safety of currently available systemic bone-targeted therapies in breast cancer patients with an emphasis on bisphosphonates and the receptor activator of nuclear factor kappa B ligand (RANKL inhibitors. We will also discuss novel strategies and therapies currently in development.

  20. Sex Differences and Bone Metastases of Breast, Lung, and Prostate Cancers: Do Bone Homing Cancers Favor Feminized Bone Marrow?

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    Mary C. Farach-Carson

    2017-08-01

    Full Text Available Sex-associated differences in bone metastasis formation from breast, lung, and prostate cancer exist in clinical studies, but have not been systematically reviewed. Differences in the bone marrow niche can be attributed to sexual dimorphism, to genetic variations that affect sex hormone levels, or to the direct effects of sex hormones, natural or exogenously delivered. This review describes the present understanding of sex-associated and sex hormone level differences in the marrow niche and in formation of bone metastasis during the transition of these three cancers from treatable disease to an often untreatable, lethal metastatic one. Our purpose is to provide insight into some underlying molecular mechanisms for hormonal influence in bone metastasis formation, and to the potential influence of sexual dimorphism, genetic differences affecting sex assignment, and sex hormone level differences on the bone niche and its favorability for metastasis formation. We reviewed publications in PubMed and EMBASE, including full length manuscripts, case reports, and clinical studies of relevance to our topic. We focused on bone metastasis formation in breast, lung, and prostate cancer because all three commonly present with bone metastases. Several clear observations emerged. For breast cancer bone metastasis formation, estrogen receptor (ER signaling pathways indicate a role for ER beta (ERβ. Estrogen influences the bone microenvironment, creating and conditioning a favorable niche for colonization and breast cancer progression. For lung cancer, studies support the hypothesis that females have a more favorable bone microenvironment for metastasis formation. For prostate cancer, a decrease in the relative androgen to estrogen balance or a “feminization” of bone marrow favors bone metastasis formation, with a potentially important role for ERβ that may be similar to that in breast cancer. Long-term estrogen administration or androgen blockade in males

  1. Sex Differences and Bone Metastases of Breast, Lung, and Prostate Cancers: Do Bone Homing Cancers Favor Feminized Bone Marrow?

    Science.gov (United States)

    Farach-Carson, Mary C; Lin, Sue-Hwa; Nalty, Theresa; Satcher, Robert L

    2017-01-01

    Sex-associated differences in bone metastasis formation from breast, lung, and prostate cancer exist in clinical studies, but have not been systematically reviewed. Differences in the bone marrow niche can be attributed to sexual dimorphism, to genetic variations that affect sex hormone levels, or to the direct effects of sex hormones, natural or exogenously delivered. This review describes the present understanding of sex-associated and sex hormone level differences in the marrow niche and in formation of bone metastasis during the transition of these three cancers from treatable disease to an often untreatable, lethal metastatic one. Our purpose is to provide insight into some underlying molecular mechanisms for hormonal influence in bone metastasis formation, and to the potential influence of sexual dimorphism, genetic differences affecting sex assignment, and sex hormone level differences on the bone niche and its favorability for metastasis formation. We reviewed publications in PubMed and EMBASE, including full length manuscripts, case reports, and clinical studies of relevance to our topic. We focused on bone metastasis formation in breast, lung, and prostate cancer because all three commonly present with bone metastases. Several clear observations emerged. For breast cancer bone metastasis formation, estrogen receptor (ER) signaling pathways indicate a role for ER beta (ERβ). Estrogen influences the bone microenvironment, creating and conditioning a favorable niche for colonization and breast cancer progression. For lung cancer, studies support the hypothesis that females have a more favorable bone microenvironment for metastasis formation. For prostate cancer, a decrease in the relative androgen to estrogen balance or a "feminization" of bone marrow favors bone metastasis formation, with a potentially important role for ERβ that may be similar to that in breast cancer. Long-term estrogen administration or androgen blockade in males may feminize the bone

  2. The Breast Cancer to Bone (B2B) Metastases Research Program: a multi-disciplinary investigation of bone metastases from breast cancer.

    Science.gov (United States)

    Brockton, Nigel T; Gill, Stephanie J; Laborge, Stephanie L; Paterson, Alexander H G; Cook, Linda S; Vogel, Hans J; Shemanko, Carrie S; Hanley, David A; Magliocco, Anthony M; Friedenreich, Christine M

    2015-07-10

    Bone is the most common site of breast cancer distant metastasis, affecting 50-70 % of patients who develop metastatic disease. Despite decades of informative research, the effective prevention, prediction and treatment of these lesions remains elusive. The Breast Cancer to Bone (B2B) Metastases Research Program consists of a prospective cohort of incident breast cancer patients and four sub-projects that are investigating priority areas in breast cancer bone metastases. These include the impact of lifestyle factors and inflammation on risk of bone metastases, the gene expression features of the primary tumour, the potential role for metabolomics in early detection of bone metastatic disease and the signalling pathways that drive the metastatic lesions in the bone. The B2B Research Program is enrolling a prospective cohort of 600 newly diagnosed, incident, stage I-IIIc breast cancer survivors in Alberta, Canada over a five year period. At baseline, pre-treatment/surgery blood samples are collected and detailed epidemiologic data is collected by in-person interview and self-administered questionnaires. Additional self-administered questionnaires and blood samples are completed at specified follow-up intervals (24, 48 and 72 months). Vital status is obtained prior to each follow-up through record linkages with the Alberta Cancer Registry. Recurrences are identified through medical chart abstractions. Each of the four projects applies specific methods and analyses to assess the impact of serum vitamin D and cytokine concentrations, tumour transcript and protein expression, serum metabolomic profiles and in vitro cell signalling on breast cancer bone metastases. The B2B Research Program will address key issues in breast cancer bone metastases including the association between lifestyle factors (particularly a comprehensive assessment of vitamin D status) inflammation and bone metastases, the significance or primary tumour gene expression in tissue tropism, the

  3. Identification of bone and liver metastases from breast cancer by measurement of plasma alkaline phosphatase isoenzyme activity.

    OpenAIRE

    Mayne, P D; Thakrar, S; Rosalki, S B; Foo, A Y; Parbhoo, S

    1987-01-01

    Plasma alkaline phosphatase isoenzyme activities were determined in patients with breast cancer to diagnose and monitor bone and liver metastases. Bone alkaline phosphatase activity was increased in 21 of 50 patients (42%) with radiologically confirmed bone metastases, while total alkaline phosphatase activity was increased in only 10 of 50 (20%); liver alkaline phosphatase activity was raised in 12 of 25 patients (48%) with liver metastases. All patients with liver metastases had bone metast...

  4. Pharmacologic management of bone-related complications and bone metastases in postmenopausal women with hormone receptor-positive breast cancer

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    Yardley DA

    2016-05-01

    Full Text Available Denise A Yardley1,2 1Sarah Cannon Research Institute, Nashville, TN, USA; 2Tennessee Oncology, Nashville, TN, USA Abstract: There is a high risk for bone loss and skeletal-related events, including bone metastases, in postmenopausal women with hormone receptor-positive breast cancer. Both the disease itself and its therapeutic treatments can negatively impact bone, resulting in decreases in bone mineral density and increases in bone loss. These negative effects on the bone can significantly impact morbidity and mortality. Effective management and minimization of bone-related complications in postmenopausal women with hormone receptor-positive breast cancer remain essential. This review discusses the current understanding of molecular and biological mechanisms involved in bone turnover and metastases, increased risk for bone-related complications from breast cancer and breast cancer therapy, and current and emerging treatment strategies for managing bone metastases and bone turnover in postmenopausal women with hormone receptor-positive breast cancer. Keywords: breast cancer, bone metastases, hormone receptor-positive, bone-related complications, interventions, management and management strategies, estrogen receptor-positive

  5. Cold metastases detected by bone scintigraphy in aggressive lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Martinez Carsi, C.; Perales Vila, A. [Servei de Medicina Nuclear de l`Hospital 9 d`Octubre, Valencia (Spain); Ruiz Hernandez, G. [Servei de Medicina Nuclear de l`Hospital Clinic Universitari, Valencia (Spain); Sanchez Marchori, C.; Oro Camps, J. [Servei de Traumatologia de l`Hospital 9 d`Octubre, Valencia (Spain)

    1998-12-31

    A case of a 55-year-old man was remitted to Traumatology Department to present back pain of two weeks of evolution. The results of bone scintigraphy and the patient`s evolution allowed the diagnosis. This case report and a literature review showed the importance of using a routine bone scan in diagnosis of bone metastases. (orig.) [Deutsch] Ein 55jaehriger Mann mit seit zwei Wochen andauernden lumbalen Schmerzen wurde in der orthopaedischen Klinik untersucht. Die Evolution des klinischen Bildes und eine Knochenszintigraphie ermoeglichten die Diagnose. Dieser klinische Fall und das wissenschaftliche Schrifttum zeigten, wie wichtig eine routinemaessige Knochenszintigraphie in der Diagnostik von Knochenmetastasen ist. (orig.)

  6. Does colon cancer ever metastasize to bone first? a temporal analysis of colorectal cancer progression

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    Gayed Isis W

    2009-08-01

    Full Text Available Abstract Background It is well recognized that colorectal cancer does not frequently metastasize to bone. The aim of this retrospective study was to establish whether colorectal cancer ever bypasses other organs and metastasizes directly to bone and whether the presence of lung lesions is superior to liver as a better predictor of the likelihood and timing of bone metastasis. Methods We performed a retrospective analysis on patients with a clinical diagnosis of colon cancer referred for staging using whole-body 18F-FDG PET and CT or PET/CT. We combined PET and CT reports from 252 individuals with information concerning patient history, other imaging modalities, and treatments to analyze disease progression. Results No patient had isolated osseous metastasis at the time of diagnosis, and none developed isolated bone metastasis without other organ involvement during our survey period. It took significantly longer for colorectal cancer patients to develop metastasis to the lungs (23.3 months or to bone (21.2 months than to the liver (9.8 months. Conclusion: Metastasis only to bone without other organ involvement in colorectal cancer patients is extremely rare, perhaps more rare than we previously thought. Our findings suggest that resistant metastasis to the lungs predicts potential disease progression to bone in the colorectal cancer population better than liver metastasis does.

  7. Characteristics and Treatment of Bone Metastases in 322 Cases Non-small Cell Lung Cancer: A Retrospective Study

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    Qingzhi GUO

    2014-09-01

    Full Text Available Background and objective Bone metastases are the most common metastases of the non-small cell lung cancer (NSCLC. It can lead to bone ache and pathology fracture, deteriorate the quality of life. Methods We retrospectively investigated the characteristics, diagnosis and prognosis factors of bone metastases in NSCLC. All of the 600 patients are from department of thoracic oncology in recently 5 years. Emission computed tomography (ECT was used to screen the bone metastases and the diagnosis of bone metastases was confirmed by computed tomography (CT/magnetic resonance imaging (MRI/X-ray or pathology. Results Among the total 322 bone metastases patients, subtype of adenocarcinoma had the most opportunity to occur bone metastases, and we found that vertebrae, pelvis and femora et al were the most frequently involved metastases sites. Patients who had more than 3 high 18F-FDG uptake sites of ECT, could be confirmed bone metastases by CT/MRI/X-ray than those with 1-2 high 18F-FDG uptake sites [80.6% (203/252 vs 50.79% (32/63, P<0.001]. The patients with bone metastases who had non-SRE had longer survival than that of SRE [1-yr survival 44.75% (non-SRE vs 36.17% (SRE; median survival 14.74 mo (non-SRE vs 12.25 mo (SRE]. Multivariables analysis showed the pathology were non-adnocarcinoma, bone metastases less than 3 sites and bone metastases without other organs metastases would have good prognosis. Conclusion There were relations between the numbers of abnormal dense sites of ECT and the diagnosis of skeletal metastases, non-adnocarcinoma bone metastases less than 3 sites and bone metastases without other organs metastases were the independent prognosis factors..

  8. Radium-223 treatment of bone metastases from castration-resistant prostate cancer

    DEFF Research Database (Denmark)

    Mortensen, Jann; Højgaard, Liselotte

    2014-01-01

    The alpha emitter Radium-223 ((22)3Ra-Cl2) is a bone-seeking radionuclide studied as a new treatment for patients with bone metastases from hormone refractory prostate cancer. More than 1,000 patients have been included in clinical phase I-III tests showing significant reduction in alkaline...

  9. Denosumab: a new option in the treatment of bone metastases from urological cancers

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    Yonese J

    2012-09-01

    Full Text Available Takeshi Yuasa, Shinya Yamamoto, Shinji Urakami, Iwao Fukui, Junji YoneseDepartment of Urology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Ariake, Tokyo, JapanAbstract: Bone metastases often create serious clinical problems: they lead to poor performance status due to pathologic fractures, spinal cord compression and intractable pain, commonly referred to as skeletal-related events. The receptor activator of nuclear factor-κB (RANK, the RANK ligand (RANKL, and osteoprotegerin, a decoy receptor for RANK, regulate osteoclastogenesis and may play a key role in bone metastasis. Denosumab (XGEVA; Amgen, Thousand Oaks, CA, a fully human monoclonal antibody that binds to and neutralizes RANKL, inhibits osteoclast function, prevents generalized bone resorption and local bone destruction, and has become a therapeutic option for preventing or delaying first on-study skeletal-related events in various malignancies. In the context of urological cancer, three main Phase III clinical studies have been published in prostate cancer. This article provides a brief overview of the characteristics of bone metastasis in urological cancers, reviews the mechanisms of bone metastasis, including the RANK/RANKL/osteoprotegerin axis, the current standard of care, zoledronic acid, and describes the efficacy of the novel bone-targeted agent denosumab in bone metastasis. Denosumab is emerging as a key therapeutic option in the treatment of bone metastases from urological cancers.Keywords: bone metastasis, denosumab, prostate cancer, renal cell cancer, urothelial cancer, zoledronic acid

  10. Emerging Lung Cancer Therapeutic Targets Based on the Pathogenesis of Bone Metastases

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    Moses O. Oyewumi

    2014-01-01

    Full Text Available Lung cancer is the second most common cancer and the leading cause of cancer related mortality in both men and women. Each year, more people die of lung cancer than of colon, breast, and prostate cancers combined. It is widely accepted that tumor metastasis is a formidable barrier to effective treatment of lung cancer. The bone is one of the frequent metastatic sites for lung cancer occurring in a large number of patients. Bone metastases can cause a wide range of symptoms that could impair quality of life of lung cancer patients and shorten their survival. We strongly believe that molecular targets (tumor-related and bone microenvironment based that have been implicated in lung cancer bone metastases hold great promise in lung cancer therapeutics. Thus, this paper discusses some of the emerging molecular targets that have provided insights into the cascade of metastases in lung cancer with the focus on bone invasion. It is anticipated that the information gathered might be useful in future efforts of optimizing lung cancer treatment strategies.

  11. Cost of palliative radiation to the bone for patients with bone metastases secondary to breast or prostate cancer

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    Hess Gregory

    2012-10-01

    Full Text Available Abstract Background To estimate the costs (paid amounts of palliative radiation episodes of care (REOCs to the bone for patients with bone metastases secondary to breast or prostate cancer. Methods Claims-linked medical records from patients at 98 cancer treatment centers in 16 US states were analyzed. Inclusion criteria included a primary neoplasm of breast or prostate cancer with a secondary neoplasm of bone metastases; ≥2 visits to ≥1 radiation center during the study period (1 July 2008 through 31 December 2009 on or after the metastatic cancer diagnosis date; radiation therapy to ≥1 bone site; and ≥1 complete REOC as evidenced by a >30-day gap pre- and post-radiation therapy. Results The total number of REOCs was 220 for 207 breast cancer patients and 233 for 213 prostate cancer patients. In the main analysis (which excluded records with unpopulated costs the median number of fractions per a REOC for treatment of metastases was 10. Mean total radiation costs (i.e., radiation direct cost + cost of radiation-related procedures and visits per REOC were $7457 for patients with breast cancer and $7553 for patients with prostate cancer. Results were consistent in sensitivity analyses excluding patients with unpopulated costs. Conclusions In the US, current use of radiation therapy for bone metastases is relatively costly and the use of multi-fraction schedules remains prevalent.

  12. Biochemical markers for assessment of bone metastases in patients with breast cancer.

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    Hou, M F; Tsai, L Y; Tsai, S M; Huang, C J; Huang, Y S; Hsieh, J S; Chan, H M; Wang, J Y; Chuang, C H; Chen, F M; Huang, T J

    1999-08-01

    Breast cancer commonly metastasizes to bones, producing both osteolytic and osteoblastic deposits. Different markers for quantitative determination of bone turnover have been developed to evaluate bone metastases of breast cancer. The urinary deoxypyridinoline (Dpd), a crosslink product of collagen molecules found in bone and excreted in urine during bone degradation, and bone specific alkaline phosphatase (B-ALP), an isoenzyme localized in the membrane of osteoblasts and released in circulation during bone formation, were recently described as a group of markers of bone turnover in metastatic cancer. The urinary Dpd/creatinine (Cre) ratios and the serum B-ALP activity were determined in the samples from 148 patients who suffered from breast cancer (BC patients) with or without bone metastases, and 42 healthy women. For comparison, other biochemical markers, e.g. carcinoembryonic antigen (CEA), CA15-3, tissue polypeptide antigen (TPA), tissue polypeptide specific antigen (TPSA), and total alkaline phosphatase (T-ALP) in these samples were also evaluated. The results showed that there was a significant difference in urinary Dpd/Cre ratio between the control group and the patients with breast cancer (BC group) (mean +/- S.D., 5.69 +/- 1.26 vs. 8.19 +/- 3.95 nM/mM, P markers, the best diagnostic efficiency of biochemical markers, analyzed by step wise discriminate analysis, was provided by CEA followed by Dpd/Cre ratio, CA15-3, TPA, TPSA, B-ALP and T-ALP. We conclude that showed the urinary Dpd/Cre ratio was a useful tumor marker to evaluate breast cancer with bone metastases.

  13. Osteoclasts Are Active in Bone Forming Metastases of Prostate Cancer Patients

    Science.gov (United States)

    Gorassini, Eva; Grimaldi, Anastasia; Bonello, Lisa; Fiori, Cristian; Delsedime, Luisa; Tizzani, Alessandro; De Libero, Alfredo; Isaia, Giancarlo; Ferracini, Riccardo

    2008-01-01

    Background Bone forming metastases are a common and disabling consequence of prostate cancer (CaP). The potential role of osteoclast activity in CaP bone metastases is not completely explained. In this study, we investigated ex vivo whether the osteolytic activity is present and how it is ruled in CaP patients with bone forming metastases. Methodology Forty-six patients affected by newly diagnosed CaP and healthy controls were enrolled. At diagnosis, 37 patients had a primary tumour only, while 9 had primary tumour and concomitant bone forming metastases. In all patients there was no evidence of metastasis to other non-bone sites. For all patients and controls we collected blood and urinary samples. We evaluated patients' bone homeostasis; we made peripheral blood mononuclear cell (PBMC) cultures to detect in vitro osteoclastogenesis; we dosed serum expression of molecules involved in cancer induced osteoclatogenesis, such as RANKL, OPG, TNF-alpha, DKK-1 and IL-7. By Real-Time PCR, we quantified DKK-1 and IL-7 gene expression on micro-dissected tumour and healthy tissue sections. Principal Findings CaP bone metastatic patients showed bone metabolism disruption with increased bone resorption and formation compared to non-bone metastatic patients and healthy controls. The CaP PBMC cultures showed an enhanced osteoclastogenesis in bone metastatic patients, due to an increase of RANKL/OPG ratio. We detected increased DKK-1 serum levels and tissue gene expression in patients compared to controls. IL-7 resulted high in patients' sera, but its tissue gene expression was comparable in patients and controls. Conclusions We demonstrated ex vivo that osteoclastogenesis is an active mechanism in tumour nesting of bone forming metastatic cancer and that serum DKK-1 levels are increased in CaP patients, suggesting to deeply investigate its role as tumour marker. PMID:18978943

  14. Effect of Bone Reading CT software on radiologist performance in detecting bone metastases from breast cancer.

    Science.gov (United States)

    Ha, Ji Y; Jeon, Kyung N; Bae, Kyungsoo; Choi, Bong H

    2017-04-01

    To evaluate the effect of CT software that generates rib unfolding images and automatically numbers ribs and thoracic spines on radiologist performance in detecting thoracic bone metastases from breast cancer. A total of 126 patients with breast cancer who underwent chest CT and fludeoxyglucose (FDG)-positron emission tomography (PET)/CT and/or bone scans were retrospectively reviewed. One board-certified radiologist (R1) and one radiology resident (R2) independently assessed the original chest CT and rib unfolding images using a commercially available post-processing software (Bone Reading) application to evaluate metastasis in the ribs and thoracic spines. Results were compared with reference standard based on CT, FDG-PET/CT and/or bone scan with follow-up. Based on reference standard, 78 metastatic bone lesions in 26 patients were identified. On per-patient-based analysis, Bone Reading assessed by R1/R2 had a sensitivity of 84.6%/80.8% and a specificity of 94.0%/94.0% with an accuracy of 92.1%/91.3%. The original CT reading yielded a sensitivity of 73.1%/57.7% and a specificity of 95.0%/94.0% with an accuracy of 90.5%/86.5%. The sensitivity and accuracy of Bone Reading were significantly higher than those of CT reading, as assessed by R2 (both p = 0.031). On per-lesion-based analysis, Bone Reading assessed by R1/R2 yielded a sensitivity of 84.6%/82.1% and a specificity of 99.7%/99.6% with an accuracy of 99.4%/99.3%, while the original CT reading yielded a sensitivity of 71.8%/62.8% and a specificity of 99.6%/99.5% with an accuracy of 99.2%/98.9%. The sensitivity and accuracy with Bone Reading application were significantly higher than those with CT reading by both readers (R1, p = 0.006 and p = 0.036, respectively; R2, both p reading time needed for Bone Reading application was significantly shorter than that for original chest CT reading (p Reading application helped readers find small and sclerotic lesions missed in original CT reading. In

  15. [Bone-specific therapy with radium-223 dichloride : Castration-resistant prostate cancer with symptomatic bone metastases].

    Science.gov (United States)

    Tauber, R; Gschwend, J; Scheidhauer, K; Eiber, M; Krönke, M

    2017-01-01

    Radium-223 dichloride (Xofigo®, Alpharadin) is approved for the treatment of metastatic castration-resistant prostate cancer with symptomatic bone metastases and no known visceral metastases. As a calcium mimetic, it is integrated into osteoplastic bone lesions and emits alpha particles with high energy which leads to local destruction of tumor cells. In the 2013 published ALSYMPCA trial, a significant advantage for overall survival and quality of life in comparison to placebo was found. Recent data suggest an increased potential in combination with next generation hormonal treatment.

  16. Integrin alpha V beta 3 expression by bone-residing breast cancer metastases.

    Science.gov (United States)

    Liapis, H; Flath, A; Kitazawa, S

    1996-06-01

    Breast cancer metastasis to bone is a multistep process requiring attachment of tumor cells to the bone and bone marrow environment. The precise adhesion molecules involved in skeletal homing of breast cancer to bone are unknown but likely include integrins. We investigated the expression of vitronectin receptor (alpha V beta 3) by breast cancer cells residing in bone because this heterodimer mediates osteoclast-bone recognition. We used immunohistochemistry and in situ hybridization in a systematic study of 22 bone biopsies containing breast cancer metastases and available samples of corresponding primary tumors and normal breast and compared alpha V beta 3, alpha 2 beta 1, and alpha B beta 5 integrin expression. The results showed that alpha V beta 3 was strongly expressed by normal breast epithelium and was decreased in some and strongly expressed in other primary invasive breast carcinomas. In contrast, this integrin heterodimer was abundant in all breast cancer cells metastatic to bone. In situ hybridization revealed high levels of steady-state mRNA corresponding to sites of protein expression; alpha 2 beta 1 was weakly expressed in both primary and metastatic tumors, and alpha V beta 5 was not detected. Our results showed an overexpression of alpha V beta 3 by bone-residing breast cancer cells and suggest either subclonal selection of alpha V beta 3-expressing tumor cell populations or upregulation of alpha V beta 3 in the bone microenvironment.

  17. Skeletal-related events due to bone metastases from differentiated thyroid cancer.

    Science.gov (United States)

    Farooki, Azeez; Leung, Vivien; Tala, Hernan; Tuttle, R Michael

    2012-07-01

    In oncology, the clinical impact of metastatic bone disease is conveyed via a composite end point termed skeletal-related events (SRE), which encompasses spinal cord compression, pathological fracture, a need for external beam radiation or surgery to bone, and hypercalcemia of malignancy. An appreciation for the high incidence of SRE in other advanced cancers involving the bone has led to the approval of potent antiresorptive agents because they delay the time to the first SRE and decrease the incidence of SRE. The risk and rate of SRE after diagnosis of bone metastasis have not been described in thyroid cancer; antiresorptive agents are not routinely used. This was a retrospective review of 245 differentiated thyroid cancer patients with bone metastases identified as part of routine clinical care at Memorial Sloan-Kettering Cancer Center between 1960 and 2011. The occurrence of SRE was recorded from the initial diagnosis of bone metastasis until final follow-up or death. Seventy-eight percent of patients (192 of 245) either presented with or developed at least one SRE after the diagnosis of metastatic bone disease. The median time from identification of bone metastasis to first SRE was 5 months (excluding the 97 patients in whom first SRE occurred at the time of the bone metastasis diagnosis). Of the patients who sustained an initial SRE, 65% (120 of 192) went on to sustain a second SRE at a median of 10.7 months after the first event. SRE were frequently multiple; 39% (74 of 192) sustained three or more discrete SRE. Thyroid cancer bone metastases identified as part of routine clinical follow-up frequently cause significant and recurrent morbidity. The incidence of SRE and median time to first SRE in metastatic thyroid cancer to bone are similar to those reported in other solid tumors. Prospective clinical trials to assess the efficacy of antiresorptive agents in this population are needed.

  18. Can surgical management of bone metastases improve quality of life among women with gynecologic cancer?

    Science.gov (United States)

    Ji, Tao; Eskander, Ramez; Wang, Yifei; Sun, Kunkun; Hoang, Bang H; Guo, Wei

    2014-08-05

    The evaluation, counseling, and management of gynecologic patients with bone metastasis remain a challenge for clinicians. In order to critically evaluate the role of surgery, we retrospectively analyzed the records of 18 patients surgically treated for metastatic gynecologic tumors of bone, focusing on quality of life, local tumor control, and survival. Eighteen patients underwent surgical procedures for the treatment of bone metastases secondary to gynecologic cancer between September 2003 and April 2012. The primary cancer sites included the uterus (n = 10), the cervix (n = 5), and an ovary (n = 3). Patients were followed for an average period of 13.8 months (range, 2 to 34 months). A visual analog pain scale (VAS) and Eastern Cooperative Oncology Group (ECOG) performance status were evaluated both pre- and postoperatively. The median survival time following diagnosis of bone metastasis was 10.0 months. The mean VAS score was 5.8 preoperatively compared with 2.1, 3 months after surgery. The mean pre and postoperative ECOG performance status grades were 3.1 and 2.3, respectively. The prognosis of gynecological cancer patients with bone metastasis is poor. Some patients had improvement in their quality of life after surgical intervention for bone metastases; however, novel integrated treatment modalities should be investigated.

  19. Cross-linked type I collagen C- and N-telopeptides in women with bone metastases from breast cancer.

    Science.gov (United States)

    Ulrich, U; Rhiem, K; Schmolling, J; Flaskamp, C; Paffenholz, I; Sälzer, H; Bauknecht, T; Schlebusch, H

    2001-01-01

    This study documents values of biochemical markers of bone remodeling in 106 patients with breast cancer. Based on scintigraphic and radiological findings, patients were divided into 3 groups: 19 patients with bone metastases, 65 patients without bone metastases and normal bone scintigrams, and 22 patients with pathological, non-malignant findings on scintigraphy without proof of bone metastases. Urinary cross-linked type I collagen N-telopeptides (NTx) and serum cross-linked type I collagen C-telopeptides (ICTP) were assessed as markers of bone resorption. Bone alkaline phosphatase (BAP) was assessed as a marker of bone formation. All three markers were significantly higher in patients with bone metastases compared to both patients without skeletal recurrence and those with pathological, non-malignant scintigraphic findings (p < 0.01). There were no statistically significant differences between the latter two groups. The clinical sensitivity for diagnosing bone metastases was 44% for NTx, 65% for ICTP, and 26% for BAP, respectively. The clinical specificitiy for discriminating patients with bone disease from those without were 79%, 91%, and 92% for NTx, ICTP, and BAP, respectively. In conclusion, markers of bone remodeling are increased in patients with breast cancer metastatic to the skeleton. The sensitivity of the markers presented in this paper did not seem to be sufficient enough for early identification of patients with subclinical bone recurrence in a clinical practice setting.

  20. Use of disodium pamidronate bisphosphonate in patients with bone metastases of lung cancer

    Directory of Open Access Journals (Sweden)

    Ranković Boško

    2002-01-01

    Full Text Available Disodium pamidronate (Aredia®, a drug of the bisphosphonate group, was administered to 20 patients with pains in the bones due to secondary deposits of lung cancer. The aim of the study was to investigate the analgesic effect of pamidronate to osteolytic metastases of lung cancer in the bone. In 16 (80% patients non-small-cell lung cancer was diagnosed, and in 4 (20% patients small-cell-lung cancer was confirmed. Intensive disseminated pains in the bones were present in all the patients. Metastases in the skeleton were confirmed by radiography and scintigraphy of the bones. Initial values of calcium in the plasma were determined in those patients. In 11 (55% patients, initial values of calcium in the serum were normal, and in 9 (45% patients, they were elevated. Patients with normal calcium values received 30 mg of pamidronate in 250 ml of normal saline, and patients with hypercalcaemia received 45-60 mg in 500 ml of normal saline. Analgesic effect of pamidronate was present in 12 (60% patients, and the completely painless state was achieved in 4 out of 12 patients. Evaluation of the pain was done by questionnaire, using a simple, descriptive scale. In all 9 (100% patients with hypercalcaemia, values of calcium in plasma were normalized. Pamidronate exerted favorable analgesic effect in the case of metastases of lung cancer in the bones in more than 50% patients. Satisfactory results were also achieved in the patients non-responsive to palliative therapy by irradiation This enables the use of opiates in lower doses.

  1. Breast cancer bone metastases: an epidemiologic study in selected radiation departments.

    Science.gov (United States)

    Runco, Raffaele; Laganà, Simona; Marino, Giacomo; Di Grazia, Alfio; Marino, Lorenza; Umina, Vincenza; Girlando, Andrea; Ricottone, Nicola; D'Agostino, Antonino; Marletta, Francesco; Tamburo, Maria; Corsaro, Giuseppe; Rallo, Francesco; Santacaterina, Anna; Acquaviva, Grazia; Crispi, Manuela; Palazzolo, Carmela; Platania, Angelo; Spatola, Corrado; Privitera, Giuseppe; Frosina, Pasquale; Garufi, Giuseppe; Bonanno, Salvatore; Rosso, Alberto; Barone, Vincenzo; Corallo, Anna; Sansotta, Giuseppe; Delia, Pietro; Donato, Valentino; Lopes, Salvatore; Pisana, Michele; Borzì, Francesca; Iatì, Giuseppe; Potami, Antonio; Messina, Giovanna; Parisi, Silvana; Frosina, Luciano; Marletta, Dario; De Renzis, Costantino; Pontoriero, Antonio; Pergolizzi, Stefano

    2014-01-01

    To quantify radiation treatments for bone metastases from breast cancer in three Sicilian provinces (Messina, Catania, Ragusa) with respect to the general population and the incidence and prevalence of breast cancer in this macro-area in a 8-year period. All bone metastasis patients treated using radiotherapy in 8 radiation departments operating in the provinces of Messina, Catania and Ragusa were collected. Among these, metastases from breast carcinoma were analyzed according to year of irradiation. An analysis of breast cancer incidence and prevalence with respect to inhabitants in this macro-area was conducted using literature and census data. From January 2004 to December 2011, irradiation was delivered in 4419 bone metastasis patients. Among these, 1617 had a primary breast cancer with a median treatment per year of 206.5 (range, 164-251); 211 patients were treated in 2004 and 206 in 2011. In 2004, there were 1,048,957 female residents in the three provinces and 1,065,422 in 2011. The reported breast cancer incidence and prevalence in Sicily was respectively 100.79/100,000 and 908.54/100,000 in 2004 and 108.41/100,000 and 1091.29/100,000 in 2010. There has been an increase in both incidence and prevalence of breast cancer in Sicily. Nevertheless, it seems that there was no increment in skeletal-related events requiring irradiation in such patients in eastern Sicily radiation departments.

  2. 18F-NaF Positive Bone Metastases of Non 18F-FDG Avid Mucinous Gastric Cancer

    OpenAIRE

    Çiğdem Soydal; Elgin Özkan; Özlem Nuriye Küçük

    2015-01-01

    Detection of gastric cancer bone metastasis is crucial since its presence is an independent prognostic factor. In this case report, we would like to present 18F-NaF positive bone metastases of non 18F-FDG avid gastric mucinous cancer.

  3. ADJUVANT TREATMENT WITH BIPHOSPONATES IN COMPLEX THERAPY OF PAPILLARY THYROID CANCER BONE METASTASES

    Directory of Open Access Journals (Sweden)

    A. D. Kaprin

    2017-01-01

    Full Text Available Distant metastasis of thyroid cancer are founded in 10% of all metastases. Bone metastases are founded in 23% of distant metastasis. Complications associated with metastatic skeletal involvement often lead to a deterioration in the overall condition and a decrease in the quality of life of patients. Surgical treatment, chemotherapy are less effective, provide a higher injury rate and toxicity. This is a reason of increasing of cost of treatment. Bisphosphonates are a class of drugs that prevent the loss of bone mass, which can prolong the time to releasing bone complications: bone fracture, spine column fracture with spinal medulla compression, which decrease the QoL. Surgical treatment and chemotherapy have worse outcomes, higher injury rate, toxicity and increase cost of treatment. Bisphosphonates decrease the level of pain syndrome. Bisphosphonates are used in treatment of oncological patients since 1990. First medication was Fosamax (Aledronat. Later more medications with better efficacy and more useful were synthesised. The last one was Zoledronic acid. Rezorba (zoledronic acid was synthesised in 2006 in Russia. Rezorba has a same efficacy with other bisphosphonates, it was shown in clinical studies with groups of breast cancer and prostatic cancer. Clinical case of 67 y.o. male patient with diagnosis: Thyroid cancer IV c st pT1bN1bM1, right neck, paratraсheal, bone and lung metastasis. Complex treatment (surgery + radioiodine therapy + 5 courses of Rezorba was presented. After 3 courses the level of pain was decreased from 3 to 1,5. After 5 courses the ECOQ score was decreased from 2 to 1 point. Inclusion of Resorba in complex treatment of patients with bone metastasis after thyroid cancer at all stages of treatment decreases the score of pain syndrome and bone tissue reparation.

  4. [Radium-223 treatment of bone metastases from castration-resistant prostate cancer].

    Science.gov (United States)

    Mortensen, Jann; Højgaard, Liselotte

    2014-07-21

    The alpha emitter Radium-223 ((22)3Ra-Cl2) is a bone-seeking radionuclide studied as a new treatment for patients with bone metastases from hormone refractory prostate cancer. More than 1,000 patients have been included in clinical phase I-III tests showing significant reduction in alkaline phosphatase- and PSA level and prolonged survival. Adverse events are usually mild to moderate and comprise gastrointestinal and myelotoxic symptoms. Intravenously administered (22)3Ra-Cl2 (half-life 11.4 days) will likely be given every four weeks for six treatments to out-patients.

  5. PREVENTION OF COMPLICATIONS IN CASTRATE-REFRACTORY PROSTATE CANCER PATIENTS WITH BONE METASTASES

    Directory of Open Access Journals (Sweden)

    K. M. Nushko

    2015-01-01

    Full Text Available Abstract:Prostate cancer (PC is one of the most urgent problems in modern oncourology. Every year the world is recording more than 900 thousands new cases of prostate cancer. For this reason, the diagnosis and treatment of this disease has recently been given more attention, both abroad and in the Russian Federation. Despite improvements in diagnostic methods and implementation of programs for active detection of the disease in its early stages, the number of patients suffering from advanced forms of prostate cancer remains high. Currently, the main method of treatment in patients with metastatic prostate cancer remains the hormone therapy (HT. Patients with metastatic prostate cancer most frequently have localization of metastatic lesions in the lymph nodes and bones. Frequent localization of metastatic lesions in the bones is due to tumor cell tropism of prostate cancer to the bone. Metastatic bone disease, as well as long-term HT conducted in patients with metastatic prostate cancer, leads to irreversible disruption of bone remodeling, which may be accompanied by osteoporosis and fragility fractures. Bone metastases in patients with PC are the most common cause of complications and significantly impair the quality of life of patients. Therapy underlying the prevention of bone complications can be specific, aimed directly at the tumor tissue and non-specific, to strengthen bones and decrease its resorption processes. The article provides an overview of the literature covering the effectiveness of modern drugs, aimed at non-specific prevention of bone complications in patients with metastatic prostate cancer, such as bisphosphonates, and inhibitors of the ligand RANKL, as well as an overview of studies to assess the effectiveness of domestic analogue zolendronovoy acid preparation Resorba in the prevention of osteoporosis.

  6. Radium-223 dichloride for the treatment of castration-resistant prostate cancer with symptomatic bone metastases.

    Science.gov (United States)

    Vogelzang, Nicholas J

    2017-08-01

    Castration-resistant prostate cancer (CRPC) is associated with the development of bone metastases, increased mortality, and a reduction in the patient's quality of life (QOL). The management of metastatic CRPC (mCRPC) has rapidly evolved over the past decade, with a number of available therapeutic agents improving overall survival. Radium-223 dichloride (radium-223), the first targeted alpha therapy, improves survival accompanied by QOL benefits with a favorable safety profile. It is approved in over 40 countries for the treatment of patients with CRPC with symptomatic bone metastases and no known visceral metastatic disease. Areas covered: The current management of CRPC in men with bone metastases, and in particular the role of radium-223 in this setting, is reviewed and discussed. A search of bibliographic databases for peer-reviewed literature and major meetings was conducted. Expert commentary: In treating patients with mCRPC, the best sequencing and/or combination of radium-223 with other agents has yet to be fully elucidated. The role of radium-223 in treating patients with hormone-sensitive metastatic prostate cancer who are candidates for chemotherapy should also be investigated in well-designed trials. The ability to tailor radium-223 therapy to both the clinical and genetic profiles of CRPC patients would be a promising development.

  7. Radium-223 chloride: Extending life in prostate cancer patients by treating bone metastases.

    Science.gov (United States)

    Wissing, Michel D; van Leeuwen, Fijs W B; van der Pluijm, Gabri; Gelderblom, Hans

    2013-11-01

    The treatment scope for patients with metastatic castrate-resistant prostate cancer (mCRPC) is rapidly expanding. On May 15, 2013, the U.S. Food and Drug Administration (FDA) approved radium-223 chloride ((223)RaCl2) for the treatment of mCRPC patients whose metastases are limited to the bones. Radium-223 is an α-emitting alkaline earth metal ion, which, similar to calcium ions, accumulates in the bone. In a phase III study (ALSYMPCA), mCRPC patients with bone metastases received best standard-of-care treatment with placebo or (223)RaCl2. At a prespecified interim analysis, the primary endpoint of median overall survival was significantly extended by 3.6 months in patients treated with radium-223 compared with placebo (P < 0.001). The radioisotope was well tolerated and gave limited bone marrow suppression. (223)RaCl2 is the first bone-targeting antitumor therapy that received FDA approval based on a significant extended median overall survival. Further studies are required to optimize its dosing and to confirm its efficacy and safety in cancer patients.

  8. Pain in castration-resistant prostate cancer with bone metastases: a qualitative study

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    Gater Adam

    2011-10-01

    Full Text Available Abstract Background Bone metastases are a common painful and debilitating consequence of castration-resistant prostate cancer (CPRC. Bone pain may predict patients' prognosis and there is a need to further explore CRPC patients' experiences of bone pain in the overall context of disease pathology. Due to the subjective nature of pain, assessments of pain severity, onset and progression are reliant on patient assessment. Patient reported outcome (PRO measures, therefore, are commonly used as key endpoints for evaluating the efficacy of CRPC treatments. Evidence of the content validity of leading PRO measures of pain severity used in CRPC clinical trials is, however, limited. Methods To document patients' experience of CRPC symptoms including pain, and their impact on health-related quality of life (HRQL, semi-structured in-depth qualitative interviews were conducted with 17 patients with CRPC and bone metastases. The content validity of the Present Pain Intensity (PPI scale from the McGill Pain Questionnaire (MPQ, and the 'Average Pain' and 'Worst Pain' items of the Brief Pain Inventory Short-Form (BPI-SF was also assessed. Results Patients with CRPC and bone metastases present with a constellation of symptoms that can have a profound effect on HRQL. For patients in this study, bone pain was the most prominent and debilitating symptom associated with their condition. Bone pain was chronic and, despite being generally well-managed by analgesic medication, instances of breakthrough cancer pain (BTcP were common. Cognitive debriefing of the selected PRO measures of pain severity highlighted difficulties among patients in understanding the verbal response scale (VRS of the MPQ PPI scale. There were also some inconsistencies in the way in which the BPI-SF 'Average Pain' item was interpreted by patients. In contrast, the BPI-SF 'Worst Pain' item was well understood and interpreted consistently among patients. Conclusions Study findings support the

  9. 68Ga-PSMA PET/CT in the evaluation of bone metastases in prostate cancer.

    Science.gov (United States)

    Sachpekidis, Christos; Bäumer, P; Kopka, K; Hadaschik, B A; Hohenfellner, M; Kopp-Schneider, A; Haberkorn, U; Dimitrakopoulou-Strauss, A

    2018-01-23

    The aims of this retrospective analysis were to compare 68Ga-PSMA PET findings and low-dose CT findings (120 kV, 30 mA), and to obtain semiquantitative and quantitative 68Ga-PSMA PET data in patients with prostate cancer (PC) bone metastases. In total, 152 PET/CT scans from 140 patients were evaluated. Of these patients, 30 had previously untreated primary PC, and 110 had biochemical relapse after treatment of primary PC. All patients underwent dynamic PET/CT scanning of the pelvis and lower abdomen as well as whole-body PET/CT with 68Ga-PSMA-11. The PET/CT scans were analysed qualitatively (visually), semiquantitatively (SUV), and quantitatively based on a two-tissue compartment model and a noncompartmental approach leading to the extraction of the fractal dimension. Differences were considered significant for p values PET-positive and CT-positive, 65 were only 68Ga-PSMA-positive, and 10 were only CT-positive. The Yang test showed that there were significantly more 68Ga-PSMA PET-positive lesions than CT-positive lesions. Association analysis showed that PSA plasma levels were significantly correlated with several 68Ga-PSMA-11-associated parameters in bone metastases, including the degree of tracer uptake (SUVaverage and SUVmax), its transport rate from plasma to the interstitial/intracellular compartment (K1), its rate of binding to the PSMA receptor and its internalization (k3), its influx rate (Ki), and its distribution heterogeneity. 68Ga-PSMA PET/CT is a useful diagnostic tool in the detection of bone metastases in PC. 68Ga-PSMA PET visualizes more bone metastases than low-dose CT. PSA plasma levels are significantly correlated with several 68Ga-PSMA PET parameters.

  10. Serum levels of PSA, ALP, ICTP, and BSP in prostate cancer patients and the significance of ROC curve in the diagnosis of prostate cancer bone metastases.

    Science.gov (United States)

    Wei, R J; Li, T Y; Yang, X C; Jia, N; Yang, X L; Song, H B

    2016-06-03

    Bone metastasis is a common complication in prostate cancer patients that can cause bone pain and pathological fracture. This study tested serum levels of prostate specific antigen (PSA), alkaline phosphatase (ALP), bone sialoprotein (BSP), collagen type I pyridine crosslinking peptide (ICTP) in prostate cancer patients and the significance of the receiver operator characteristic (ROC) curve in the diagnosis of prostate cancer bone metastases. Eighty-three prostate cancer patients were enrolled including 42 in the bone metastases group and 41 in the non-bone metastases group. Serum levels of BSP, ALP, ICTP, and PSA were highest in the bone metastases group followed by the non-bone metastases group, hyperplasia group, and then the control group (P Gleason score, serum levels were highest in the poorly differentiated group followed by moderately differentiated and well-differentiated groups (P bone metastases were 80.95, 57.14, 69.05, 71.43%, respectively, and the specificity of the same markers were 72.80, 64.80, 76.80, and 88.80%, respectively. Combined detection of the four markers improved sensitivity to 97.62% and the negative-predictive value increased to 97.60%. PSA + BSP showed the best efficiency when combining two markers. In conclusion, serum levels of BSP, ALP, ICTP, and PSA increased in patients with bone metastases, and combined detection of all markers could improve the positive-predictive value.

  11. Management of bone metastases in refractory prostate cancer – role of denosumab

    Directory of Open Access Journals (Sweden)

    Paller CJ

    2012-09-01

    Full Text Available Channing J Paller,1 Michael A Carducci,1 George K Philips21Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA; 2Georgetown Lombardi Comprehensive Cancer Center, Washington DC, USAAbstract: This article reviews the problem of bone disease in prostate cancer and the evolving role of the novel agent denosumab, a fully human monoclonal antibody that inhibits the receptor activator of nuclear factor-ΚB ligand, in suppressing bone resorption and offering bone protection in this disease. Prostate cancer frequently metastasizes to bone, and additionally its treatment with androgen deprivation leads to accelerated bone loss resulting in clinically relevant skeletal complications associated with disabling symptoms. Among the bone-targeting therapeutic strategies investigated for the prevention of bone complications, the potent bisphosphonate zoledronic acid has been the most widely used agent for bone protection in the past decade. Denosumab is the first among a new class of osteoclast-targeting agents to show superior efficacy in several clinical scenarios in both prostate and breast cancer, as well as in osteoporosis, but the focus of this review will be on its role in prostate cancer. The safety and efficacy of denosumab versus zoledronic acid was established in a randomized trial, demonstrating a delay in skeletal-related events in metastatic castration-resistant prostate cancer patients. This study led to the approval of denosumab in the US. The chief risks of denosumab were hypocalcemia and osteonecrosis of the jaw. Denosumab was also approved for fracture risk reduction in patients on androgen-deprivation therapy for nonmetastatic prostate cancer. Although denosumab extended bone metastasis-free survival in a Phase III trial in men with castration-resistant nonmetastatic prostate cancer to a statistically significant degree, a Food and Drug Administration committee found that the effect was not sufficiently clinically

  12. Ca2+ Receptor, Prostate Cancer, and Bone Metastases

    Science.gov (United States)

    2005-03-01

    the skeletal complications of metastatic niurie hyperealcemia andother syndromes ofaltered respansive- breast cancer and on the incidence of new... dhat an hicrease in extra.ehlinlar Ca42 resulted :in delayed activation of exlracellular signal-regulated kinwse (ERK) in PC-3 cells. Pre-intcubation

  13. The Difficult Task of Diagnosing Prostate Cancer Metastases on Dry Bone.

    Science.gov (United States)

    Castoldi, Elisa; Cappella, Annalisa; Gibelli, Daniele; Sforza, Chiarella; Cattaneo, Cristina

    2017-08-17

    The interpretation of pathology on skeletal remains is mandatory for implementing the biological profile and for disease recognition. Prostate cancer is one of the most common tumors, with a high preference for the skeleton as a primary site of metastasis. Its diagnosis on bone is however still ambiguous, due to its "osteoblastic" and resorptive manifestation. This study investigates distribution and appearance of prostate cancer metastases on dry bone on six known cases (selected from the Milano Cemetery Skeletal Collection) and one healthy individual. A macroscopic inspection was performed highlighting the abnormalities observed, describing location, shape, dimension, and aspect. A great amount of proliferative and mixed lesions was noticed, but also cases of pure lytic lesions were displayed. The multiple appearances of the manifestations observed display the difficulty in correctly identifying such a pathology, but also the potential and advantages provided by investigating a study sample with known antemortem history. © 2017 American Academy of Forensic Sciences.

  14. Different patterns of change in bone turnover markers during treatment with bone-modifying agents for breast cancer patients with bone metastases.

    Science.gov (United States)

    Nishimukai, Arisa; Higuchi, Tomoko; Ozawa, Hiromi; Yanai, Ayako; Miyagawa, Yoshimasa; Murase, Keiko; Imamura, Michiko; Takatsuka, Yuichi; Miyoshi, Yasuo

    2017-03-01

    Bone-modifying agents are effective for treatment of breast cancer patients with bone metastases. Since their action is mediated through suppression of the osteoclast function, their efficacy can be determined by monitoring bone turnover markers. However, the clinical significance of these markers is yet to be compared. For this study, 52 breast cancer patients with bone metastases treated with zoledronic acid (n = 36) or denosumab (n = 22) were enrolled (6 patients were treated sequentially with both agents). Serum tartrate-resistant acid phosphatase-5b (TRACP-5b), pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (1CTP), N-terminal cross-linking telopeptides of type I collagen (NTX) and bone-specific alkaline phosphatase (BAP) were measured at pretreatment and 1, 3 and 6 months after treatment. Serum TRACP-5b (p agents reduced the baseline levels of TRACP-5b, NTX and BAP significantly, the reduction patterns differed. TRACP-5b appears to affect levels most quickly and sensitively, possibly due to its direct link to the number and activity of osteoclasts. These findings suggest that the efficacy of TRACP-5b is clinically significant when considering which bone-modifying agents to use for breast cancer patients with bone metastases.

  15. [Radiotherapy of bone metastases].

    Science.gov (United States)

    Thureau, S; Vieillard, M-H; Supiot, S; Lagrange, J-L

    2016-09-01

    Radiotherapy plays a major role in palliative treatment of bone metastases. Recent developments of stereotactic radiotherapy and intensity modulated radiation therapy give the possibility to treat oligometastatic diseases. The objective of this paper is to report indications and treatment modalities of radiotherapy in these situations. Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

  16. Evaluation of Prostate Cancer Bone Metastases with 18F-NaF and 18F-Fluorocholine PET/CT.

    Science.gov (United States)

    Beheshti, Mohsen; Rezaee, Alireza; Geinitz, Hans; Loidl, Wolfgang; Pirich, Christian; Langsteger, Werner

    2016-10-01

    18F-fluorocholine is a specific promising agent for imaging tumor cell proliferation, particularly in prostate cancer, using PET/CT. It is a beneficial tool in the early detection of marrow-based metastases because it excludes distant metastases and evaluates the response to hormone therapy. In addition, 18F-fluorocholine has the potential to differentiate between degenerative and malignant osseous abnormalities because degenerative changes are not choline-avid; however, the agent may accumulate in recent traumatic bony lesions. On the other hand, 18F-NaF PET/CT can indicate increased bone turnover and is generally used in the assessment of primary and secondary osseous malignancies, the evaluation of response to treatment, and the clarification of abnormalities on other imaging modalities or clinical data. 18F-NaF PET/CT is a highly sensitive method in the evaluation of bone metastases from prostate cancer, but it has problematic specificity, mainly because of tracer accumulation in degenerative and inflammatory bone diseases. In summary, 18F-NaF PET/CT is a highly sensitive method, but 18F-fluorocholine PET/CT can detect early bone marrow metastases and provide greater specificity in the detection of bone metastases in patients with prostate cancer. However, the difference seems not to be significant. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  17. Betulinic acid, a bioactive pentacyclic triterpenoid, inhibits skeletal-related events induced by breast cancer bone metastases and treatment

    Energy Technology Data Exchange (ETDEWEB)

    Park, Se Young; Kim, Hyun-Jeong; Kim, Ki Rim; Lee, Sun Kyoung; Lee, Chang Ki; Park, Kwang-Kyun, E-mail: biochelab@yuhs.ac; Chung, Won-Yoon, E-mail: wychung@yuhs.ac

    2014-03-01

    Many breast cancer patients experience bone metastases and suffer skeletal complications. The present study provides evidence on the protective and therapeutic potential of betulinic acid on cancer-associated bone diseases. Betulinic acid is a naturally occurring triterpenoid with the beneficial activity to limit the progression and severity of cancer, diabetes, cardiovascular diseases, atherosclerosis, and obesity. We first investigated its effect on breast cancer cells, osteoblastic cells, and osteoclasts in the vicious cycle of osteolytic bone metastasis. Betulinic acid reduced cell viability and the production of parathyroid hormone-related protein (PTHrP), a major osteolytic factor, in MDA-MB-231 human metastatic breast cancer cells stimulated with or without tumor growth factor-β. Betulinic acid blocked an increase in the receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin ratio by downregulating RANKL protein expression in PTHrP-treated human osteoblastic cells. In addition, betulinic acid inhibited RANKL-induced osteoclastogenesis in murine bone marrow macrophages and decreased the production of resorbed area in plates with a bone biomimetic synthetic surface by suppressing the secretion of matrix metalloproteinase (MMP)-2, MMP-9, and cathepsin K in RANKL-induced osteoclasts. Furthermore, oral administration of betulinic acid inhibited bone loss in mice intra-tibially inoculated with breast cancer cells and in ovariectomized mice causing estrogen deprivation, as supported by the restored bone morphometric parameters and serum bone turnover markers. Taken together, these findings suggest that betulinic acid may have the potential to prevent bone loss in patients with bone metastases and cancer treatment-induced estrogen deficiency. - Highlights: • Betulinic acid reduced PTHrP production in human metastatic breast cancer cells. • Betulinic acid blocked RANKL/OPG ratio in PTHrP-stimulated human osteoblastic cells. • Betulinic

  18. Mechanisms of Radiation-Induced Bone Loss and Effects on Prostate Cancer Bone Metastases

    Science.gov (United States)

    2013-06-01

    skeletal sites. Indeed, within five years of radiation treatment at the pelvic region ( cervical , rectal or anal cancer), the risk of hip fracture ...radiation-induced effects at skeletal sites, including bone loss and increased fracture risk at the hip [2-4]. Indeed, the risk of hip fracture within...general population [5-7]. Hip fracture causes considerable morbidity and mortality to cancer patients during the course of treatment and poses a

  19. THE DIAGNOSTIC EFFICACY OF SPECT/CT IN DETECTION OF BONE METASTASES IN PATIENTS WITH BREAST AND PROSTATE CANCER

    Directory of Open Access Journals (Sweden)

    Е. А. Glushkov

    2015-01-01

    Full Text Available The present study was undertaken to evaluate the benefit of single photon emission computed tomography/ computed tomography (SPECT/CT over SPECT alone, osteoscintigraphy (OSG, CT and conventional X-ray for the detection of bone metastasis in patients with breast cancer (BC and prostate cancer (PC. 72 BC patients and 17 PC patients at high risk of developing bone metastasis were examined by (SPECT/ CT, SPECT,OSG,CTand conventional X-ray. Bone metastases were detected in 33 (37.1 % patients. It was found that the diagnostic efficacy (sensitivity, specificity and accuracy of SPECT/CT was significantly superior to that of the other types of imaging modalities in detection of bone metastases from BC. In addition, the combination of SPECT with CT resulted in a change in SPECT and CT findings on skeletal metastasis in 5 (6 % and 11 (12 % cases, respectively.

  20. Infiltrating Mast Cells Correlate with Angiogenesis in Bone Metastases from Gastric Cancer Patients

    Directory of Open Access Journals (Sweden)

    Michele Ammendola

    2015-02-01

    Full Text Available While gastric cancer is a well established angiogenesis driven tumor, no data has been published regarding angiogenesis stimulated by mast cells (MCs positive for tryptase in bone metastases from gastric cancer patients (BMGCP. It is well established that MCs play a role in immune responses and more recently it was demonstrated that MCs have been involved in tumor angiogenesis. We analyzed infiltrating MCs and neovascularization in BMGCP diagnosed by histology. A series of 15 stage T3-4N2-3M1 (by AJCC for Gastric Cancer Staging 7th Edition BMGCP from bone biopsies were selected. Tumour tissue samples were evaluated by mean of immunohistochemistry and image analysis methods in terms of MCs density positive to tryptase (MCDPT, MCs area positive to tryptase (MCAPT, microvascular density (MVD and endothelial area (EA. A significant correlation between MCDPT, MCAPT, MVD and EA groups to each other was found by Pearson and t-test analysis (r ranged from 0.68 to 0.82; p-value ranged from 0.00 to 0.02. Our very preliminary data suggest that infiltrating MCs positive for tryptase may play a role in BMGCP angiogenesis, and could be further evaluated as a novel target of anti-angiogenic therapy.

  1. The effects of denosumab on calcium profiles in advanced cancer patients with bone metastases.

    Science.gov (United States)

    Lechner, Breanne; DeAngelis, Carlo; Jamal, Noreen; Emmenegger, Urban; Pulenzas, Natalie; Giotis, Angie; Sheehan, Parker; Tsao, May; Bedard, Gillian; Chow, Edward

    2014-07-01

    To retrospectively examine the incidence and management of hypocalcemia for patients with bone metastases treated with denosumab. Patients who had a record of filling a prescription of denosumab for treatment of bone metastases at the outpatient pharmacy at the Odette Cancer Centre from May 2011 to February 2013 were included in the analysis. Demographic information, previous bisphosphonate usage, calcium and albumin values, and adverse events were obtained using the Sunnybrook Electronic Patient Record system (EPR) and the Oncology Symptom Control and Information Resource (OSCIR). Hypocalcemia was defined as a calcium value below 2.0 mmol/L within a 28-day±7-day window after the last injection of denosumab based on the Common Terminology Criteria for Adverse Events (CTCAE) grade 2 hypocalcemia. A total of 55 patients had record of a prescription for denosumab filled with an average age of 62 years (range 40 to 93 years), 18 (32.7%) were males and 37 (67.3%) were females. Twenty-nine (52.7%) patients had primary breast cancer, 12 (21.8%) prostate, 10 (18.2%) lung, and 4 (7.3%) with other types. Using CTCAE grading of hypocalcemia, 17 (32.7%) patients experienced grade 1, 4 (7.7%) patients grade 2, 4 (7.7%) patients grade 3, and 1 (1.9%) patient grade 4. The number of injections before the incident of hypocalcemia was a median of one injection (range 1 to 14). Time from the first hypocalcemia lab value to normocalcemia was a median of 33 days. This study found that 9 of 52 (17.3%) patients had at least one incidence of hypocalcemia of grade 2 or higher after receiving denosumab. Cautionary measures should be taken to avoid hypocalcemia in patients receiving denosumab.

  2. A multicentre observational study of radionuclide therapy in patients with painful bone metastases of prostate cancer.

    Science.gov (United States)

    Dafermou, A; Colamussi, P; Giganti, M; Cittanti, C; Bestagno, M; Piffanelli, A

    2001-07-01

    A multicentre observational study was conducted by the Italian Association of Nuclear Medicine between 1996 and 1998. Twenty-nine Nuclear Medicine Departments participated. The aims of the study were to systematically evaluate the efficacy, toxicity and repeatability of radionuclide therapy of painful bone metastases (RTBM) in a large number of patients and to assess its incidence in patients with prostate cancer. Out of 818 treatments performed with a single i.v. dose of 148 MBq of strontium-89 chloride or 1,295 MBq of rhenium-186 hydroxyethylidene diphosphonate (HEDP), 610 could be evaluated (527 with 89Sr and 83 with 186Re-HEDP). Eighty-one patients received multiple (up to five) RTBM. The total number of retreatments was 100. Patients were followed up for a period of 3-24 months. Results, assessed according to pain relief and consumption of analgesic drugs, were expressed at four levels: 1, no response; 2, mild response; 3, good response; 4, excellent response. Responses were: level 1 in 19%, level 2 in 21.3%, level 3 in 33.3% and level 4 in 26.4% of cases. Retreatments showed significantly (P<0.01) worse responses (48% levels 3+4), in comparison to first RTBM. Duration of palliation was 5.0+/-3.5 months, and was longer in cases of excellent response, in first RTBM, in patients with limited metastases and when 89Sr was used. Better responses were found in cases of limited skeletal disease, under good clinical conditions, when life expectancy exceeded 3 months, and in radiologically osteoblastic or mixed bone lesions. The only statistically significant predictive factor was life expectancy (P<0.001). Flare phenomenon (14.1% of cases) did not correlate with the response. Haematological toxicity (mild to moderate in most cases) mainly affected platelets, and was observed in 25.5% of cases overall and in 38.9% of retreatments. RTBM did not seem to prolong life, though in some cases scintigraphic regression of bone metastases was observed. The two

  3. Detection and correlation analysis of serum cytokines in non-small-cell lung cancer patients with bone and non-bone metastases

    Directory of Open Access Journals (Sweden)

    Sun Y

    2015-08-01

    Full Text Available Yingjia Sun, Xinghao Ai, Shengping Shen, Linping Gu, Shun Lu Lung Tumor Clinical Medical Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China Objective: To detect and analyze 13 cytokines that may be related to bone metastasis in the serum of non-small-cell lung cancer (NSCLC patients with bone metastases and NSCLC patients with non-bone metastases.Patients and methods: The Luminex LiquiChip system was used to detect the concentration of 13 cytokines that may be related to bone metastasis in the serum of 30 NSCLC patients with bone metastases and 30 with non-bone metastases.Results: The concentration of insulin-like growth factor binding protein-3 (IGFBP-3 in the serum of NSCLC patients with bone metastases was obviously higher than in non-bone metastasis patients (P=0.014. The serum concentration of other cytokines showed no significant difference (P>0.05 between the two groups. The concentration of IGFBP-3 in the serum of the bone metastasis group was positively correlated to VEGF concentration (r=0.804, P=0.009 and monocyte chemotactic protein 1 (MCP-1 concentration (r=0.785, P=0.012, but had no correlation to other factors (P>0.05. No correlation was found between serum concentrations of cytokines in bone metastasis. Concentration of IGFBP-3 in the serum of bone metastasis patients was positively correlated to the presence or absence of pain at diagnosis (r=0.701, P=0.036 and performance status (PS score (r=0.670, P=0.048, and correlated with the number of bone metastases, sex, age, pathological characteristics, T stage, and N stage (P>0.05.Conclusion: The findings of this study suggest important clinical implications to detect the concentration of IGFBP-3 in the serum of lung cancer patients so as to evaluate the diagnosis and degree of bone metastasis. Concentration of IGFBP-3 in the serum of bone metastasis patients was positively correlated to concentration of VEGF and MCP-1, which may be

  4. Risk Factors for Developing Skeletal-Related Events in Breast Cancer Patients With Bone Metastases Undergoing Treatment With Bone-Modifying Agents.

    Science.gov (United States)

    Tanaka, Ryota; Yonemori, Kan; Hirakawa, Akihiro; Kinoshita, Fumie; Takahashi, Naoki; Hashimoto, Jun; Kodaira, Makoto; Yamamoto, Harukaze; Yunokawa, Mayu; Shimizu, Chikako; Fujimoto, Manabu; Fujiwara, Yasuhiro; Tamura, Kenji

    2016-04-01

    Bone-modifying agents (BMAs) reduce the incidence of skeletal-related events (SREs) and are thus recommended for breast cancer patients with bone metastases. However, the risk factors for SREs during BMA treatment are not well-understood. This study evaluated the number and timing of SREs from case studies to identify these factors. The medical records of 534 women with breast cancer who developed bone metastases between 1999 and 2011 were reviewed. SREs were defined as a pathologic fracture, spinal cord compression, or the need for bone irradiation or surgery. Multiple variables were assessed and were analyzed by using the Cox proportional hazard analyses and the Andersen and Gill method. Multivariate analyses for both the time to the first SRE and the primary and subsequent SRE frequency demonstrated that significant baseline risk factors included luminal B type disease, a history of palliative radiation therapy, BMA treatment within 2 years, and elevated serum calcium levels at the time of the initial BMA dose. Additionally, for the time to the first SRE and for the primary and subsequent SRE frequency, the presence of extraskeletal metastases and BMA administration initiation ≥6 months after the detection of bone metastases were also significant risk factors, respectively. In breast cancer patients with bone metastases, more vigilant observation should be considered for patients with the identified risk factors. To reduce the risk for SRE, BMAs should be administered within 6 months of bone metastases diagnosis and before palliative radiation therapy. Retrospectively, risk factors were identified for skeletal-related events (SREs) in breast cancer patients with bone metastasis who were treated with bone-modifying agents (BMAs). For the time to the first SRE and for the SRE frequency, presence of extraskeletal metastases and BMA initiation ≥6 months after the detection of bone metastases were risk factors, respectively. Luminal B type disease, a history of

  5. Detection of bone metastases in breast cancer patients in the PET/CT era: Do we still need the bone scan?

    Science.gov (United States)

    Caglar, M; Kupik, O; Karabulut, E; Høilund-Carlsen, P F

    2016-01-01

    To examine the value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for the detection of bone metastasis in breast cancer patients and assess whether whole body bone scan (BS) with (99m)Tc-methylene diphosphonate provides any additional information. Study group comprised 150 patients, mean age 52 years (range 27-85) with breast cancer, suspected of having bone metastases. All patients had undergone both FDG-PET/CT and BS with or without single photon emission tomography/computed tomography (SPECT/CT) within a period of 6 weeks. The final diagnosis of bone metastasis was established by histopathological findings, additional imaging, or clinical follow-up longer than 10 months. Cancer antigen 15-3 (CA15-3) and carcinoembryogenic antigen (CEA) were measured in all patients. Histologically 83%, 7% and 10% had infiltrating ductal, lobular and mixed carcinoma respectively. Confirmed bone metastases were present in 86 patients (57.3%) and absent in 64 (42.7%). Mean CA15-3 and CEA values in patients with bone metastases were 74.6ng/mL and 60.4U/mL respectively, compared to 21.3ng/mL and 3.2U/mL without metastases (p<0.001). The sensitivity of FDG-PET/CT for the detection of bone metastases was 97.6% compared to 89.5% with SPECT/CT. In 57 patients, FDG-PET/CT correctly identified additional pulmonary, hepatic, nodal and other soft tissue metastases, not detected by BS. Our findings suggest that FDG-PET/CT is superior to BS with or without SPECT/CT. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

  6. Use of denosumab in a dialysis patient with bone metastases from breast cancer and hepatorenal polycystic disease: a case report.

    Science.gov (United States)

    Quiroga García, Vanesa; Cirauqui Cirauqui, Beatriz; Tobey Robaina, Lyan; López Sisamon, David; Hardy-Werbin, Max; Blanca, Ana Belén; Margelí Vila, Mireia

    2016-06-01

    Cancer patients with severe renal dysfunction represent a challenge for the physician. This is the first case report on the use of denosumab in a dialysis patient with bone metastases. We present the clinical case of a 45-year-old woman who had hepatorenal polycystic disease, diagnosed during childhood, and stage IV chronic kidney failure at the time of breast cancer diagnosis. Three years after surgery plus adjuvant hormonal therapy she suffered a further worsening of renal function, requiring dialysis, and very advanced bone metastasis in the hip with severe pain. As pamidronate was the only bone agent available in the center, she received it for 4 months (before a dialysis session), during which time the bone metastases stabilized. In March 2014, the patient switched to denosumab (which had become available in the center), and continued with hormone therapy. Seven months after denosumab initiation, the patient had almost complete pain relief, and the bone metastases exhibited radiological improvement. The tolerability was excellent, without any related adverse event. There were no changes in albumin-adjusted serum calcium, serum phosphorus, and intact parathyroid hormone, except for a transient and mild hypocalcemia at 3 months and an increase in intact parathyroid hormone levels, which required adjustment of vitamin D analog dose. Denosumab can be administered to prevent skeletal-related events in patients with bone metastasis from solid tumors and severely impaired renal function, even in those requiring dialysis. In this particular patient, the safety was good.

  7. Treatment of bone metastases of prostate cancer with strontium-89 chloride: efficacy in relation to the degree of bone involvement

    Energy Technology Data Exchange (ETDEWEB)

    Kraeber-Bodere, F.; Campion, L.; Rousseau, C.; Bourdin, S.; Chatal, J.-F.; Resche, I. [Rene Gauducheau Cancer Center, Nantes (France)

    2000-10-01

    This retrospective study evaluated the toxicity and efficacy of strontium-89 chloride (Metastron, Amersham) in 94 patients with painful bone metastases of prostate cancer (117 injections of 150 MBq) and compared the efficacy of treatment in patients with moderate and extensive bone involvement. The predictive value of flare response with regard to analgesic response was also studied. High-grade leukothrombopenians were observed after only 5% of injections. An improvement in quality of life was obtained in 65% of cases, a decrease in pain in 78% (31% complete response) and a reduction of analgesics in 60%. Efficacy was significantly better for pain decrease (P=0.005) and reduction of analgesics (P=0.018), and response was significantly longer (P<0.0035) in patients with moderate than in patients with extensive bone involvement. The flare response observed in 23% of cases was not predictive of pain response (P=0.919) or reduction of analgesics (P=0.353). A second dose prolonged analgesia in three-quarters of cases without any apparent increase in toxicity. These results confirm the benefit of {sup 89}Sr chloride for the treatment of metastatic bone pain and suggest that internal radiotherapy should be started earlier. A bone scan could be proposed at the time of hormonal escape resulting in bone pain, and internal radiotherapy could be initiated when several metastatic foci exist, even if only one is painful. In this way, pain-free follow-up could be prolonged, and the transition to other therapeutic approaches, particularly opioids, delayed. (orig.)

  8. Prostate Cancer Metastases to Bone: Role of High Bone Turnover Induced by Androgen Deprivation

    National Research Council Canada - National Science Library

    Padalecki, Susan

    2002-01-01

    .... Treatment with androgen deprivation therapy leads to an increase in bone turnover as indicated by the loss of bone mineral density and the increase in markers of bone turnover in patients on treatment...

  9. Prostate Cancer Metastases Alter Bone Mineral and Matrix Composition Independent of Effects on Bone Architecture in Mice A Quantitative Study Using microCT and Raman Spectroscopy

    Science.gov (United States)

    Bi, Xiaohong; Sterling, Julie A.; Merkel, Alyssa R.; Perrien, Daniel S.; Nyman, Jeffry; Mahadevan-Jansen, Anita

    2013-01-01

    Prostate cancer is the most common primary tumor and the second leading cause of cancer-related deaths in men in the United States. Prostate cancer bone metastases are characterized by abnormal bone remodeling processes and result in a variety of skeletal morbidities. Prevention of skeletal complications is a crucial element in prostate cancer management. This study investigated prostate cancer-induced alterations in the molecular composition and morphological structure of metastasis-bearing bones in a mouse model of prostate cancer using Raman spectroscopy and micro-computed tomography (microCT). LNCaP C4-2B prostate cancer cells were injected into the right tibiae of 5-week old male SCID mice. Upon sacrifice at 8 weeks post tumor inoculation, two out of the ten tumor-bearing tibiae showed only osteoblastic lesions in the radiographs, 4 osteolytic lesions only and 4 mixed with osteoblastic and osteolytic lesions.. Carbonate substitution was significantly increased while there was a marked reduction in the level of collagen mineralization, mineral crystallinity, and carbonate:matrix ratio in the cortex of the intact tumor-bearing tibiae compared to contralateral controls. MicroCT analysis revealed a significant reduction in bone volume/total volume, trabecular number and trabecular thickness, as well as significant increase in bone surface/volume ratio in tibiae with osteolytic lesions, suggesting active bone remodeling and bone loss. None of the changes in bone compositional properties were correlated with lesion area from radiographs or the changes in bone architecture from microCT. This study indicates that LNCaP C4-2B prostate cancer metastases alter bone tissue composition independent of changes in architecture, and altered bone quality may be an important contributor to fracture risk in these patients. Raman spectroscopy may provide a new avenue of investigation into interactions between tumor and bone microenvironment. PMID:23867219

  10. Phase II study of concurrent capecitabine and external beam radiotherapy for pain control of bone metastases of breast cancer origin.

    Directory of Open Access Journals (Sweden)

    Yulia Kundel

    Full Text Available Pain from bone metastases of breast cancer origin is treated with localized radiation. Modulating doses and schedules has shown little efficacy in improving results. Given the synergistic therapeutic effect reported for combined systemic chemotherapy with local radiation in anal, rectal, and head and neck malignancies, we sought to evaluate the tolerability and efficacy of combined capecitabine and radiation for palliation of pain due to bone metastases from breast cancer.Twenty-nine women with painful bone metastases from breast cancer were treated with external beam radiation in 10 fractions of 3 Gy, 5 fractions a week for 2 consecutive weeks. Oral capecitabine 700 mg/m(2 twice daily was administered throughout radiation therapy. Rates of complete response, defined as a score of 0 on a 10-point pain scale and no increase in analgesic consumption, were 14% at 1 week, 38% at 2 weeks, 52% at 4 weeks, 52% at 8 weeks, and 48% at 12 weeks. Corresponding rates of partial response, defined as a reduction of at least 2 points in pain score without an increase in analgesics consumption, were 31%, 38%, 28%, 34% and 38%. The overall response rate (complete and partial at 12 weeks was 86%. Side effects were of mild intensity (grade I or II and included nausea (38% of patients, weakness (24%, diarrhea (24%, mucositis (10%, and hand and foot syndrome (7%.External beam radiation with concurrent capecitabine is safe and tolerable for the treatment of pain from bone metastases of breast cancer origin. The overall and complete response rates in our study are unusually high compared to those reported for radiation alone. Further evaluation of this approach, in a randomized study, is warranted.ClinicalTrials.gov NCT01784393NCT01784393.

  11. Pathologic fracture and metastatic spinal cord compression in patients with prostate cancer and bone metastases

    Directory of Open Access Journals (Sweden)

    Haukland Ellinor

    2010-12-01

    Full Text Available Abstract Background The purpose of this study was to determine the risk factors for and incidence as well as prognostic impact of pathologic fracture (PF and metastatic spinal cord compression (MSCC in patients with bone metastases (BM from prostate cancer. Methods Retrospective cohort study including 61 consecutive patients seen at Nordland hospital's department of oncology between 2007 and 2009. The initial diagnosis of BM might have been made earlier. Twenty-nine patients (48% received taxotere and 72% zoledronic acid after diagnosis of BM. Results Median actuarial survival after diagnosis of BM was 23 months. Six patients (10% were alive at 5 years. Bone pain at baseline was present in 49% of patients. Eighty-nine percent required external beam radiotherapy and/or radioisotopes after diagnosis of BM. Seventeen patients (28% developed at least one major skeletal complication, i.e. MSCC or PF (4 of them developed more than one. The actuarial risk was 44% at 4 and 5 years. Most events developed before treatment with zoledronic acid and/or taxotere. Median survival from diagnosis of either MSCC or PF was 11 months (5 months from MSCC. We did not identify statistically significant risk factors for development of major skeletal complications. Serum alkaline phosphatase above median value and age less than or equal to 70 years were the only risk factors approaching significance. Conclusions We found high rates of major skeletal complications in this unselected contemporary group of patients. Identification of risk factors might guide the development of early interventions aiming at prevention of MSCC and PF.

  12. Musculoskeletal Complications and Bone Metastases in Breast Cancer Patients Undergoing Estrogen Deprivation Therapy

    Science.gov (United States)

    2015-10-01

    multiple myeloma, as compared to non-tumor control mice, had lower ex vivo muscle -specific force of the EDL (measured in the contralateral limb ), and...oxidized RyR1 channels leaked Ca2+, resulting in lower intracellular signaling, which is required for proper muscle contraction. We found that...ventricle and found that these mice had bone metastases, lower skeletal muscle mass and reduced body weight, fat and lean content (Supplementary

  13. Prognostic value of the bone scan index using a computer-aided diagnosis system for bone scans in hormone-naive prostate cancer patients with bone metastases.

    Science.gov (United States)

    Miyoshi, Yasuhide; Yoneyama, Shuko; Kawahara, Takashi; Hattori, Yusuke; Teranishi, Jun-ichi; Kondo, Keiichi; Moriyama, Masatoshi; Takebayashi, Shigeo; Yokomizo, Yumiko; Yao, Masahiro; Uemura, Hiroji; Noguchi, Kazumi

    2016-02-19

    The bone scan index (BSI) using a computer-aided diagnosis system for bone scans is expected to be an objective and quantitative clinical tool for evaluating bone metastatic prostate cancer. This study aimed to evaluate the pretreatment BSI as a prognostic factor in hormone-naive prostate cancer patients with bone metastases. The study included 60 patients with hormone-naive, bone metastatic prostate cancer that was initially treated with combined androgen blockade therapy. The BONENAVI system was used for calculating the BSI. We evaluated the correlation between overall survival (OS) and pretreatment clinicopathological characteristics, including patients' age, initial prostate-specific antigen (PSA) value, Gleason scores, clinical TNM stage, and the BSI. Cox proportional hazards regression models were used for statistical analysis. The median follow-up duration was 21.4 months. Clinical or PSA progression occurred in 37 (61.7%) patients and 18 (30.0%) received docetaxel. Death occurred in 16 (26.7%) patients. Of these deaths, 15 (25.0%) were due to prostate cancer. The median OS was not reached. In multivariate analysis, age and the BSI were independent prognostic factors for OS. We evaluated the discriminatory ability of our models, including or excluding BSI by quantifying the C-index. The BSI improved the C-index from 0.751 to 0.801 for OS. Median OS was not reached in patients with a BSI ≤ 1.9 and median OS was 34.8 months in patients with a BSI >1.9 (p = 0.039). The pretreatment BSI and patients' age are independent prognostic factors for patients with hormone-naive, bone metastatic prostate cancer.

  14. SU-D-303-01: Spatial Distribution of Bone Metastases In Metastatic Castrate-Resistant Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Perk, T; Bradshaw, T; Harmon, S; Perlman, S; Liu, G; Jeraj, R [University of Wisconsin, Madison, WI (United States)

    2015-06-15

    Purpose: Identification of metastatic bone lesions is critical in prostate cancer, where treatments may be more effective in patients with fewer lesions. This study aims characterize the distribution and spread of bone lesions and create a probability map of metastatic spread in bone. Methods: Fifty-five metastatic castrate-resistant prostate cancer patients received up to 3 whole-body [F-18]NaF PET/CT scans. Lesions were identified by physician on PET/CT and contoured using a threshold of SUV>15. An atlas-based segmentation method was used to create CT regions, which determined skeletal location of lesions. Patients were divided into 3 groups with low (N<40), medium (40100) numbers of lesions. A combination of articulated and deformable registrations was used to register the skeletal segments and lesions of each patient to a single skeleton. All the lesion data was then combined to make a probability map. Results: A total of 4038 metastatic lesions (mean 74, range 2–304) were identified. Skeletal regions with highest occurrence of lesions included ribs, thoracic spine, and pelvis with 21%, 19%, and 15% of the total number lesions and 8%, 18%, and 31 % of the total lesion volume, respectively. Interestingly, patients with fewer lesions were found to have a lower proportion of lesions in the ribs (9% in low vs. 27% in high number of lesions). Additionally, the probability map showed specific areas in the spine and pelvis where over 75% of patients had metastases, and other areas in the skeleton with a less than 2% of metastases. Conclusion: We identified skeletal regions with higher incidence of metastases and specific sub-regions in the skeleton that had high or low probability of occurrence of metastases. Additionally, we found that metastatic lesions in the ribs and skull occur more commonly in advanced disease. These results may have future applications in computer-aided diagnosis. Funding from the Prostate Cancer Foundation.

  15. Survival and prognostic factors in non-small cell lung cancer patients with spinal bone metastases. A retrospective analysis of 303 patients

    Energy Technology Data Exchange (ETDEWEB)

    Rief, H.; Welzel, T.; Rieken, S.; Bischof, M.; Lindel, K.; Combs, S.E.; Debus, J. [University Hospital of Heidelberg, Department of Radiation Oncology, Heidelberg (Germany); Muley, T. [University Hospital of Heidelberg, Thorax Clinic, Department of Thoracic Oncology, Heidelberg (Germany); Bruckner, T. [University Hospital of Heidelberg, Department of Medical Biometry, Heidelberg (Germany)

    2014-01-15

    For palliative care of spinal bone metastases, stability assessment is of crucial importance. Pathological fractures, instability-related patient immobility and the extent of bone metastasis have been reported to affect patient outcome and these parameters have therefore been used for treatment stratification. We report on stability-dependent fracture and survival rates in over 300 non-small cell lung cancer (NSCLC) patients. Data from 303 patients with 868 osteolytic metastases treated with radiotherapy (RT) between 2000 and 2012 were evaluated retrospectively. In NSCLC patients with bone metastases only, the retrospective 6- and 12-month overall survival (OS) rates were 76.7 and 47.2%, respectively. In patients with additional non-bone distant metastases, these values were 60.0 and 34.0%, respectively. Survival rates were significantly lower in patients with multiple bone metastases and in those suffering pathological fractures (p=0.017). No significant impact of histological type, location of spinal lesions or treatment regime was detected. Furthermore, stability assessment revealed no influence of vertebral column stability on patient outcome (p=0.739). Our analysis demonstrated a correlation between the pathological fractures of bone lesions, the number of bone metastases, additional distant metastases and survival. The results offer a rationale for future prospective investigations. (orig.)

  16. Incidence of bone metastases and skeletal-related events in breast cancer patients: A population-based cohort study in Denmark

    Directory of Open Access Journals (Sweden)

    Fryzek Jon P

    2011-01-01

    Full Text Available Abstract Background Breast cancer (BrCa is the most commonly diagnosed cancer among women in the industrialized world. More than half of women presenting with metastatic BrCa develop bone metastases. Bone metastases increase the risk of skeletal-related events (SREs, defined as pathological fractures, spinal cord compression, bone pain requiring palliative radiotherapy, and orthopaedic surgery. Both bone metastases and SREs are associated with unfavorable prognosis and greatly affect quality of life. Few epidemiological data exist on SREs after primary diagnosis of BrCa and subsequent bone metastasis. We therefore estimated the incidence of bone metastases and SREs in newly-diagnosed BrCa patients in Denmark from 1999 through 2007. Methods We estimated the overall and annual incidence of bone metastases and SREs in newly-diagnosed breast cancer patients in Denmark from January 1, 1999 to December 31, 2007 using the Danish National Patient Registry (DNPR, which covers all Danish hospitals. We estimated the cumulative incidence of bone metastases and SREs and associated 95% confidence intervals (CI using the Kaplan-Meier method. Results Of the 35,912 BrCa patients, 178 (0.5% presented with bone metastases at the time of primary breast cancer diagnosis, and of these, 77 (43.2% developed an SRE during follow up. A total of 1,272 of 35,690 (3.6% BrCa patients without bone metastases at diagnosis developed bone metastases during a median follow-up time of 3.4 years. Among these patients, 590 (46.4% subsequently developed an SRE during a median follow-up time of 0.7 years. Incidence rates of bone metastases were highest the first year after the primary BrCa diagnosis, particularly among patients with advanced BrCa at diagnosis. Similarly, incidence rates of a first SRE was highest the first year after first diagnosis of a bone metastasis. Conclusions The high incidence of SREs following the first year after first diagnosis of a bone metastasis

  17. N-Telopeptide of Type I Collagen Long-Term Dynamics in Breast Cancer Patients With Bone Metastases: Clinical Outcomes and Influence of Extraskeletal Metastases.

    Science.gov (United States)

    Ferreira, Arlindo R; Alho, Irina; Shan, Ning; Matias, Margarida; Faria, Mariana; Casimiro, Sandra; Leitzel, Kim; Ali, Suhail; Lipton, Allan; Costa, Luís

    2016-12-01

    Markers of bone metabolism, such as N-telopeptide of type I collagen (NTX), have been demonstrated to be prognostic in previous trials of breast cancer (BC) patients with bone metastases (BMs). In the present study, we tested the survival effect of the NTX response to zoledronic acid (ZA) at 3 and 12 months in a contemporaneous cohort of BC patients with BMs and evaluated the influence of extraskeletal metastatic disease on NTX variation. The present study was a prospective cohort study of consecutive BC patients diagnosed and treated at a single center. Patients presenting with de novo radiological evidence of BMs who started monthly intravenous ZA were included. Urinary NTX was measured at baseline and 1, 3, 6, 9, and 12 months after ZA introduction. Overall, 71 patients were enrolled, 32 with BMs and 39 with BMs plus extraskeletal metastases. The proportion of patients with elevated NTX at baseline and 3 and 12 months was 49.3%, 26.6%, and 34.2%, respectively. The variables associated with survival included age at diagnosis, tumor estrogen receptor status, and NTX at 3 and 12 months. Multivariate analysis showed that, in addition to age at diagnosis, only the 3-month NTX level was significantly associated with survival. Patients with BMs plus extraskeletal metastases had an erratic NTX variation pattern, unrelated to survival. In the present contemporaneous cohort of BC patients with BMs, the NTX response at 3 months was strongly associated with survival. Furthermore, an early response to ZA was strongly associated with long-term NTX control. Finally, patients with BMs plus extraskeletal metastases had an erratic NTX variation. The present study showed that when accommodating recent therapy innovations and longer patient survival, the N-telopeptide (NTX) variation at 3 months is strongly associated with survival. In this setting, in addition to a few other clinicopathological features, NTX is a powerful prognostic marker. Moreover, early NTX correction

  18. Utilization of bone densitometry for prediction and administration of bisphosphonates to prevent osteoporosis in patients with prostate cancer without bone metastases receiving antiandrogen therapy

    Science.gov (United States)

    Holt, Abby; Khan, Muhammad A; Gujja, Swetha; Govindarajan, Rangaswmy

    2015-01-01

    Background Prostate cancer subjects with prostate-specific antigen (PSA) relapse who are treated with androgen deprivation therapy (ADT) are recommended to have baseline and serial bone densitometry and receive bisphosphonates. The purpose of this community population study was to assess the utilization of bone densitometry and bisphosphonate therapy in men receiving ADT for non-metastatic prostate cancer. Methods A cohort study of men aged 65 years or older with non-metastatic incident diagnoses of prostate cancer was obtained from the Surveillance Epidemiology End Results (SEER)-linked Medicare claims between 2004 and 2008. Claims were used to assess prescribed treatment of ADT, bone densitometry, and bisphosphonates. Results A total of 30,846 incident prostate cancer cases receiving ADT and aged 65 years or older had no bone metastases; 87.3% (n=26,935) on ADT did not receive either bone densitometry or bisphosphonate therapy. Three percent (n=931) of the cases on ADT received bisphosphonate therapy without ever receiving bone densitometry, 8.8% (n=2,702) of the cases on ADT received bone densitometry without receiving intravenous bisphosphonates, while nearly 1% (0.90%, n=278) of the cases on ADT received both bone densitometry and bisphosphonates. Analysis showed treatment differed by patient characteristics. Conclusion Contrary to the recommendations, bone densitometry and bisphosphonate therapy are underutilized in men receiving ADT for non-metastatic prostate cancer. PMID:25565887

  19. MR-HIFU for treatment of painful bone metastases

    NARCIS (Netherlands)

    Huisman, M.

    2014-01-01

    Purpose: Bone metastases are the most common cause of pain in cancer patients. Palliative radiotherapy is effective in relieving pain in bone metastases and has been the standard of care for decades. Nevertheless, an increasing amount of patients is insufficiently palliated by radiotherapy alone.

  20. Repeatability of quantitative parameters of 18F-fluoride PET/CT and biochemical tumour and specific bone remodelling markers in prostate cancer bone metastases.

    Science.gov (United States)

    Wassberg, Cecilia; Lubberink, Mark; Sörensen, Jens; Johansson, Silvia

    2017-12-01

    18F-fluoride PET/CT exhibits high sensitivity to delineate and measure the extent of bone metastatic disease in patients with prostate cancer. 18F-fluoride PET/CT could potentially replace traditional bone scintigraphy in clinical routine and trials. However, more studies are needed to assess repeatability and biological uptake variation. The aim of this study was to perform test-retest analysis of quantitative PET-derived parameters and blood/serum bone turnover markers at the same time point. Ten patients with prostate cancer and verified bone metastases were prospectively included. All underwent two serial 18F-fluoride PET/CT at 1 h post-injection. Up to five dominant index lesions and whole-body 18F-fluoride skeletal tumour burden were recorded per patient. Lesion-based PET parameters were SUVmax, SUVmean and functional tumour volume applying a VOI with 50% threshold (FTV50%). The total skeletal tumour burden, total lesion 18F-fluoride (TLF), was calculated using a threshold of SUV of ≥15. Blood/serum biochemical bone turnover markers obtained at the time of each PET were PSA, ALP, S-osteocalcin, S-beta-CTx, 1CTP and BAP. A total of 47 index lesions and a range of 2-122 bone metastases per patient were evaluated. Median time between 18F-fluoride PET/CT was 7 days (range 6-8 days). Repeatability coefficients were for SUVmax 26%, SUVmean 24%, FTV50% for index lesions 23% and total skeletal tumour burden (TLF) 35%. Biochemical bone marker repeatability coefficients were for PSA 19%, ALP 23%, S-osteocalcin 18%, S-beta-CTx 22%, 1CTP 18% and BAP 23%. Quantitative 18F-fluoride uptake and simultaneous biochemical bone markers measurements are reproducible for prostate cancer metastases and show similar magnitude in test-retest variation.

  1. Radium-223 dichloride: a review of its use in patients with castration-resistant prostate cancer with symptomatic bone metastases.

    Science.gov (United States)

    Shirley, Matt; McCormack, Paul L

    2014-04-01

    Radium-223 dichloride (Xofigo®; formerly Alpharadin™) [hereafter referred to as radium-223] is a first-in-class alpha particle-emitting radiopharmaceutical that has recently been approved for the treatment of patients with castration-resistant prostate cancer (CRPC) with symptomatic bone metastases and no known visceral metastatic disease. Radium-223 is a calcium mimetic, which targets bone, delivering cytotoxic radiation to the sites of bone metastases. In the recently reported Alpharadin™ in Symptomatic Prostate Cancer (ALSYMPCA) phase III study, radium-223 was associated with significantly improved overall survival compared with placebo, making it the first bone-targeted CRPC therapy for which an overall survival benefit has been demonstrated. The ALSYMPCA study also demonstrated the beneficial effects of radium-223 on disease-related symptomatic skeletal events, pain and health-related quality of life. Radium-223 was generally well tolerated, being associated with low rates of myelosuppression and generally mild gastrointestinal adverse events. Thus, radium-223 is a valuable addition to the treatment options for this poor-prognosis population.

  2. Bone pain palliation with Strontium-89 in cancer patients with bone metastases

    Energy Technology Data Exchange (ETDEWEB)

    Giammarile, F. [Centre Leon Berard, Dept. of Nuclear Medicine, Lyon (France); Mognetti, T. [Centre Hospitalier Universitaire Edouard Herriot, Lyon (France); Resche, I. [Centre Rene Gauducheau, Nantes (France)

    2001-03-01

    Strontium-89 is s pure {beta}-emitting radioisotope, a chemical analogue of calcium, and it is therefore avidly concentrated by areas of high osteoblastic activity. Selective uptake and prolonged retention at sites of increased bone mineral turnover provide precise bone lesions targeting. {sup 89}Sr chloride (commercialised as Metastron(R)) is typically administered in a single 150 MBq parenteral dose. Its radioactive emission poses very little radioprotection concerns. Overall, studies show pain relief in up to 80% of patients, of which 10 to 40% became effectively pain free. The mean duration of palliation was 3-4 months. The mechanism of pain relief is controversial; it is probably, but not only, related to the absorbed dose in the tumor and bone. There is no clear dose-response relationship. The only reported toxicity is temporary myelosuppression. WBC and platelets should be monitored at least on a weekly basis until they return to baseline. It seems that only patients with a reasonably good general condition stand to benefit from this treatment. In conclusion, systemic radionuclide therapy using {sup 89}Sr represents a feasible, safe, effective, well tolerated and cost-effective palliative treatment in patients with refractory bone pain.

  3. DEGRO practice guidelines for palliative radiotherapy of metastatic breast cancer. Bone metastases and metastatic spinal cord compression (MSCC)

    Energy Technology Data Exchange (ETDEWEB)

    Souchon, Rainer [Dept. of Radiation Oncology, UKT Tuebingen (Germany); Wenz, Frederik [Univ. Hospital Mannheim (Germany); Sedlmayer, Felix [Univ. Hospital, Salzburger Landeskliniken, Salzburg (Austria); Budach, Wilfried [Univ. Hospital Duesseldorf (Germany); Dunst, Juergen [Univ. Hospital Schleswig-Holstein, Luebeck (Germany); Feyer, Petra [Klinikum Neukoelln, Berlin (Germany); Haase, Wulf [St.-Vincentius-Kliniken, Karlsruhe (Germany); Harms, Wolfgang [St. Clara Hospital, Basel (Switzerland); Sautter-Bihl, Marie-Luise [Municipal Hospital, Karlsruhe (Germany); Sauer, Rolf [Univ. Hospital Erlangen (Germany)

    2009-07-15

    To provide practice guidelines and clinical recommendations on preferred standard palliative radiation therapy of bone metastases as well as metastatic spinal cord compression (MSCC) for metastatic breast cancer patients. Methods: The breast cancer expert panel of the German Society of Radiation Oncology (DEGRO) performed a comprehensive survey of the literature comprising recently published data from clinical controlled trials. The literature search encompassed the period 1995-2008 using databases of PubMed and Guidelines International Network (G-I-N). Search terms were ''breast cancer'', ''bone metastasis'', ''osseous metastasis'', ''metastatic spinal cord compression'' as well as ''radiotherapy'' and ''radiation therapy''. Clinical recommendations were formulated based on the panel's interpretation of the level of evidence referring to the criteria of evidence-based medicine. Results: Different therapeutic goals (pain relief, local tumor control, prevention or improvement of motor deficits, stabilization of the spine or other bones) require complex approaches considering individual factors (i.e. life expectancy, tumor progression at other sites). Best results are achieved by close interdisciplinary cooperation minimizing the interval between diagnosis and onset of treatment. Most important criteria for prognosis and choice of treatment (mostly combined multimodal therapy) are neurologic status at diagnosis of MSCC, time course of duration and progression of the neurologic symptoms. Radiation therapy is effective and regarded as treatment of choice for MSCC with or without motor deficits and/or bone metastases, which do not need immediate surgical intervention. It may be used either postoperatively or as primary treatment in case of inoperability. An optimal dose fractionation schedule or optimal standard dose for treatment of bone

  4. Diagnostic performance of 11C-choline PET/CT and bone scintigraphy in the detection of bone metastases in patients with prostate cancer.

    Science.gov (United States)

    Kitajima, Kazuhiro; Fukushima, Kazuhito; Yamamoto, Shingo; Kato, Takashi; Odawara, Soichi; Takaki, Haruyuki; Fujiwara, Masayuki; Yamakado, Koichiro; Nakanishi, Yukako; Kanematsu, Akihiro; Nojima, Michio; Hirota, Shozo

    2017-08-01

    The aim of this study was to compare 11C-choline PET/CT and bone scintigraphy (BS) for detection of bone metastases in patients with prostate cancer. Twenty-one patients with histologically proven prostate cancer underwent 11C-choline PET/CT and BS before (n = 4) or after (n = 17) treatment. Patient-, region-, and lesion-based diagnostic performances of bone metastasis of both 11C-choline PET/CT and BS were evaluated using a five-point scale by two experienced readers. Bone metastases were present in 11 (52.4%) of 21 patients and 48 (32.7%) of 147 regions; 111 lesions were found to have bone metastases. Region-based analysis showed that the sensitivity, specificity, accuracy, and area under the receiver-operating-characteristic curves (AUC) of 11C-choline PET/CT were 97.9%, 99.0%, 98.6%, and 0.9989, respectively; those of BS were 72.9%, 99.0%, 90.5%, and 0.8386, respectively. Sensitivity, accuracy, and AUC significantly differed between the two methods (McNemar test, p = 0.0015, p = 0.0015, and p PET/CT detected 110/111 metastatic lesions (99.1%); BS detected 85 (76.6%) (p PET/BS were 100%/90.3% for the blastic type, 91.7%/8.3% for the lytic type, 100%/100% for the mixed type, and 100%/53.3% for the invisible type, respectively. Significant differences in blastic, lytic, and invisible types were observed between the two methods (p = 0.013, p = 0.0044, and p = 0.023, respectively). In conclusion, 11C-choline PET/CT had greater sensitivity and accuracy than BS for detection of bone involvement in patients with prostate cancer.

  5. [Alpha emitter radium-223 dichloride: new therapy in castration-resistant prostate cancer with symptomatic bone metastases].

    Science.gov (United States)

    Heinzer, H; König, F; Klutmann, S

    2014-04-01

    Radium-223 dichloride (Ra-223) is an alpha emitter with low toxicity for the treatment of patients with castrations-resistant prostate cancer (CRPC) and symptomatic bone metastases showing a 30% reduction in the risk of death, as compared to placebo. Because of the favorable physical and chemical characteristics, Ra-223 can be handled easily in daily practice based on interdisciplinary co-operation between urology and nuclear medicine. Ra-223 has been approved under the product name Xofigo® by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA).

  6. Comparison of choline-PET/CT, MRI, SPECT, and bone scintigraphy in the diagnosis of bone metastases in patients with prostate cancer: a meta-analysis

    Energy Technology Data Exchange (ETDEWEB)

    Shen, Guohua; Deng, Houfu; Hu, Shuang; Jia, Zhiyun [West China Hospital of Sichuan University, Department of Nuclear Medicine, Chengdu, Sichuan (China)

    2014-11-15

    Published data on the diagnosis of bone metastases of prostate cancer are conflicting and heterogeneous. We performed a comprehensive meta-analysis to compare the diagnostic performance of choline-PET/CT, MRI, bone SPECT, and bone scintigraphy (BS) in detecting bone metastases in parents with prostate cancer. Pooled sensitivity, specificity, and diagnostic odds ratios (DOR) were calculated both on a per-patient basis and on a per-lesion basis. Summary receiver operating characteristic (SROC) curves were also drawn to obtain the area under curve (AUC) and Q* value. Sixteen articles consisting of 27 studies were included in the analysis. On a per-patient basis, the pooled sensitivities by using choline PET/CT, MRI, and BS were 0.91 [95 % confidence interval (CI): 0.83-0.96], 0.97 (95 % CI: 0.91-0.99), 0.79 (95 % CI: 0.73-0.83), respectively. The pooled specificities for detection of bone metastases using choline PET/CT, MRI, and BS, were 0.99 (95 % CI: 0.93-1.00), 0.95 (95 % CI: 0.90-0.97), and 0.82 (95 % CI: 0.78-0.85), respectively. On a per-lesion basis, the pooled sensitivities of choline PET/CT, bone SPECT, and BS were 0.84 (95 % CI: 0.81-0.87), 0.90 (95 % CI: 0.86-0.93), 0.59 (95 % CI: 0.55-0.63), respectively. The pooled specificities were 0.93 (95 % CI: 0.89-0.96) for choline PET/CT, 0.85 (95 % CI: 0.80-0.90) for bone SPECT, and 0.75 (95 % CI: 0.71-0.79) for BS. This meta-analysis indicated that MRI was better than choline PET/CT and BS on a per-patient basis. On a per-lesion analysis, choline PET/CT with the highest DOR and Q* was better than bone SPECT and BS for detecting bone metastases from prostate cancer. (orig.)

  7. Factors that predict the development of bone metastases due to prostate cancer: Recommendations for follow-up and therapeutic options.

    Science.gov (United States)

    Rodríguez-Antolín, A; Gómez-Veiga, F; Alvarez-Osorio, J K; Carballido-Rodriguez, J; Palou-Redorta, J; Solsona-Narbón, E; Sánchez-Sánchez, E; Unda, M

    2014-05-01

    Prostate cancer is a public health problem in Spain and in the Western world. Bone involvement, associated to significant morbidity, is practically constant in the advanced stages of the disease. This work aims to review the prognostic factors used in the usual clinical practice that predict the development of bone metastases and to analyze the follow-up and treatment option in these patient profiles. We performed a review of the literature on the useful factors in the context of therapy with intention to cure. We included the classical clinical values in the diagnosis (PSA, clinical stage, Gleason score on the biopsy) pathological factors (pT stage, margins, bladder invasion, tumor volume, lymph node involvement) and PSA kinetics in their different contexts and the histological and molecular parameters. The tumor differentiation "Gleason" score and PSA are the most important predictive factors in the prediction of bone metastases in patients with intention to cure. Kinetic factors such as PSA doubling time (TDPSA) 10 ng/ml in the case of castration-resistant prostate cancer (CPRC), are predictive factors for the development of metastasis. Zoledronic acid and denosumab have demonstrated their effectiveness for the treatment of bone disease in randomized studies. There are predictive factors within the usual clinical practice that make it possible to recognize the "patient at risk" to develop bone metastatic disease. The currently available treatments, zoledronic acid or denosumab, can help us in the management of the patient at risk of developing metastasis or metastatic patient, increasing the quality of life and decreasing skeletal events. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

  8. Radium-223 dichloride: a novel treatment option for castration-resistant prostate cancer patients with symptomatic bone metastases.

    Science.gov (United States)

    McGann, Shane; Horton, Evan R

    2015-04-01

    To review and evaluate the clinical trial efficacy and safety of radium 223 ((223)Ra) along with its place in therapy in men with castration-resistant prostate cancer (CRPC). A literature search in PubMed/MEDLINE (up to October 2014) was performed using various combinations of the terms radium, hormone-refractory prostate cancer, and castration-resistant prostate cancer. The New Drug Application Medical, Pharmacology, and Clinical Pharmacology and Biopharmaceutics Reviews for radium (223)Ra dichloride were also utilized. The bibliographies of articles were reviewed to identify additional references. Phase 1, 2, and 3 studies that assessed the safety and/or efficacy of (223)Ra in patients with CRPC were reviewed. Peer-reviewed articles with clinically relevant information were reviewed for background information. In May 2013, the Food and Drug Administration approved intravenous use of (223)Ra for the treatment of patients with CRPC, symptomatic bone metastases, and no known visceral metastatic disease. In a phase 3 study comparing (223)Ra and the best standard of care (SOC) versus the best SOC plus placebo, (223)Ra was shown to increase survival. The most commonly seen adverse drug reactions and hematological laboratory abnormalities with (223)Ra include nausea, diarrhea, vomiting, peripheral edema, anemia, lymphocytopenia, leukopenia, thrombocytopenia, and neutropenia. (223)Ra is a first-in-class α-particle-emitting radioactive agent that is first-line therapy, providing an extra option for men suffering from CRPC with symptomatic bone metastases and no known visceral metastases. (223)Ra has also been shown to be relatively well tolerated when up to 6 injections are given. Further studies are needed to evaluate whether (223)Ra is safe and effective for more than 6 doses and if it can be used concomitantly with chemotherapy. © The Author(s) 2015.

  9. A metastatic castration resistant prostate cancer patient with multiple bone metastases has durable biochemical and radiological response to docetaxel chemotherapy

    Science.gov (United States)

    Daimon, Tatsuaki; Kosaka, Takeo; Oya, Mototsugu

    2016-01-01

    Docetaxel chemotherapy for metastatic castration resistant prostate cancer patients has been thought palliative because the radiological response rate is low and durable response is rare. The patient was a 64-year-old man who was diagnosed with cT3aN0M0 prostate cancer and underwent external beam radiation therapy as the initial treatment. He underwent androgen deprivation therapy and 8 cycles of docetaxel chemotherapy. His PSA level decreased and became undetectable and the disease was confirmed to be stable by radiological examination. We report a rare case that a metastatic castration resistant prostate cancer patient with multiple bone metastases has durable radiological and biochemical response. PMID:27766278

  10. Utilization of bone densitometry for prediction and administration of bisphosphonates to prevent osteoporosis in patients with prostate cancer without bone metastases receiving antiandrogen therapy

    Directory of Open Access Journals (Sweden)

    Holt A

    2014-12-01

    Full Text Available Abby Holt,1 Muhammad A Khan,2 Swetha Gujja,3 Rangaswmy Govindarajan31Arkansas Department of Health, Little Rock, 2White River Health System, Batesville, 3Division of Hematology/Oncology, University of Arkansas for Medical Sciences, Little Rock, AR, USABackground: Prostate cancer subjects with prostate-specific antigen (PSA relapse who are treated with androgen deprivation therapy (ADT are recommended to have baseline and serial bone densitometry and receive bisphosphonates. The purpose of this community population study was to assess the utilization of bone densitometry and bisphosphonate therapy in men receiving ADT for non-metastatic prostate cancer.Methods: A cohort study of men aged 65 years or older with non-metastatic incident diagnoses of prostate cancer was obtained from the Surveillance Epidemiology End Results (SEER-linked Medicare claims between 2004 and 2008. Claims were used to assess prescribed treatment of ADT, bone densitometry, and bisphosphonates.Results: A total of 30,846 incident prostate cancer cases receiving ADT and aged 65 years or older had no bone metastases; 87.3% (n=26,935 on ADT did not receive either bone densitometry or bisphosphonate therapy. Three percent (n=931 of the cases on ADT received bisphosphonate therapy without ever receiving bone densitometry, 8.8% (n=2,702 of the cases on ADT received bone densitometry without receiving intravenous bisphosphonates, while nearly 1% (0.90%, n=278 of the cases on ADT received both bone densitometry and bisphosphonates. Analysis showed treatment differed by patient characteristics.Conclusion: Contrary to the recommendations, bone densitometry and bisphosphonate therapy are underutilized in men receiving ADT for non-metastatic prostate cancer.Keywords: prostatic neoplasms, androgen antagonists, bone densitometry, gonadotropin-releasing hormone, osteoporosis

  11. Prostate cancer in patients from rural and suburban areas – PSA value, Gleason score and presence of metastases in bone scan

    Directory of Open Access Journals (Sweden)

    Wojciech Szot

    2014-11-01

    Full Text Available [b]Introduction[/b]. Prostate cancer is the second most common neoplasm among men both worldwide and in Poland. In prostate cancer, bone metastasis is related to a poorer prognosis. A diagnosis of metastatic bone disease is important in prostate cancer patients prior to therapy. Prostate specific antigen (PSA serum value is used both as a screening tool and for staging of prostate cancer. aim. To evaluate whether there is a link between symptoms presented by patients, pain in particular, and the presence, number and location of bone metastases as assessed by bone scan scintigraphy in concordance with PSA values and Gleason scores. [b]material[/b]. A group of 186 patients (aged: 68.38±6.16 diagnosed with prostate cancer, from rural and suburban areas of Małopolska province, that was directed for bone scan scintigraphy to the Nuclear Medicine Dept, John Paul II Hospital in Kraków. [b]methods[/b]. Analysis of all laboratory findings (including PSA value and a biopsy were performed. Then, bone scan scintigraphy was done with the use of methylene disphosphonate (MDP labeled with Tc-99m. [b]results[/b]. In patients with a Gleason value ≤7 and a PSA value ≤20 ng/ml, the cutoff value for a negative bone scan with a confidence interval of 0.95 was established at a PSA value below 10 ng/ml (p<0.01. Correlations were established between PSA value and presence of metastases in bone scan (r=0.45, p=0.05, the number of metastases (r=0.66, p<0.01, and their presence in particular body regions. [b]conclusions[/b]. The correlation between PSA value and both presence and number of metastases confirms the usefulness of bone scan scintigraphy in prostate cancer staging. The cutoff value for negative bone scan with a 95% confidence interval was established at PSA = 10 ng/ml.

  12. Inguinal metastases from testicular cancer

    DEFF Research Database (Denmark)

    Daugaard, Gedske; Karas, Vladimir; Sommer, Peter

    2006-01-01

    To evaluate the incidence of inguinal metastases in patients with testicular cancer and relapse after initial stage I disease.......To evaluate the incidence of inguinal metastases in patients with testicular cancer and relapse after initial stage I disease....

  13. A Rare Case: Gastric Cancer; Involving Primery Thoracal Vertebral Metastases

    Directory of Open Access Journals (Sweden)

    Harun Arslan

    2013-06-01

    Full Text Available Primery bone metastases rarely occur in gastric cancer. Bone metastases indicate that the prognosis is bad. In that article we present a case that is diagnosed as a gastric cancer with primary bone metasteses that caused pathologic thoracal vertebral fracture seenby computer ised tomography.

  14. (153)Sm-EDTMP for pain relief of bone metastases from prostate and breast cancer and other malignancies.

    Science.gov (United States)

    Correa-González, Luis; Arteaga de Murphy, Consuelo; Pichardo-Romero, Pablo; Pedraza-López, Martha; Moreno-García, Claudia; Correa-Hernández, Luis

    2014-05-01

    Approximately 85% of patients with cancer suffer severe metastatic bone pain for which radionuclide therapy has been employed for pain palliation. We undertook this study to evaluate the pain relief effect of (153)Sm-EDTMP in Mexican patients with severe and painful bone metastases from mainly prostate, breast, and renal cancer and other malignancies. Patients (277) with intense sustained pain caused by bone metastases were referred to the Nuclear Medicine Department of the Oncology Hospital of the Mexican Social Security Institute. The patients had to have acceptable physical conditions, a previous positive (99m)Tc-MDP scan and blood values within normal range. (153)Sm-EDTMP was prepared at the Instituto Nacional de Investigaciones Nucleares (ININ) and 37 MBq/kg of body weight was injected intravenously. Pain palliation was evaluated with a visual analogue scale (VAS) and a verbal rating scale (VRS) before treatment and 3 and 12 weeks after treatment was started. The age interval of the patients was 24-92 years with a mean age of 64 ± 12 years. Mean values for hemoglobin, leukocyte and platelet counts did not statistically differ at zero time, 3 and 12 weeks after treatment. Pain intensity and relief assessment were statistically different: 9.1 ± 0.61 units initially; 4.2 ± 1.3 units 3 weeks later (54%) and after 12 weeks the pain diminished to 2.4 ± 1.4 units (74%) in the pain relief score scales. (153)Sm-EDTMP was readily available, safe and well tolerated. We conclude that (153)Sm-EDTMP was an adequate palliative agent and was the best option for our Mexican patients to relieve their severe metastatic bone pain. Copyright © 2014 IMSS. Published by Elsevier Inc. All rights reserved.

  15. Diffusion-weighted imaging and dynamic contrast-enhanced MRI of experimental breast cancer bone metastases – A correlation study with histology

    Energy Technology Data Exchange (ETDEWEB)

    Merz, Maximilian [Department of Medical Physics in Radiology, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Department of Hematology, Oncology and Rheumatology, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg (Germany); Seyler, Lisa; Bretschi, Maren; Semmler, Wolfhard [Department of Medical Physics in Radiology, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Bäuerle, Tobias, E-mail: tobias.baeuerle@uk-erlangen.de [Department of Medical Physics in Radiology, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Institute of Radiology, University Medical Center Erlangen, Palmsanlage 5, 90154 Erlangen (Germany)

    2015-04-15

    Purpose: To validate imaging parameters from diffusion-weighted imaging and dynamic contrast-enhanced MRI with immunohistology and to non-invasively assess microstructure of experimental breast cancer bone metastases. Materials and methods: Animals bearing breast cancer bone metastases were imaged in a clinical 1.5 T MRI scanner. HASTE sequences were performed to calculate apparent diffusion coefficients. Saturation recovery turbo FLASH sequences were conducted while infusing 0.1 mmol/l Gd–DTPA for dynamic contrast-enhanced MRI to quantify parameters amplitude A and exchange rate constant k{sub ep}. After imaging, bone metastases were analyzed immunohistologically. Results: We found correlations of the apparent diffusion coefficients from diffusion-weighted imaging with tumor cellularity as assessed with cell nuclei staining. Histological vessel maturity was correlated negatively with parameters A and k{sub ep} from dynamic contrast-enhanced MRI. Tumor size correlated inversely with cell density and vessel permeability as well as positively with mean vessel calibers. Parameters from the rim of bone metastases differed significantly from values of the center. Conclusion: In vivo diffusion-weighted imaging and dynamic contrast-enhanced MRI in experimental bone metastases provide information about tumor cellularity and vascularity and correlate well with immunohistology.

  16. [Percutaneous radiotherapy of bone metastases].

    Science.gov (United States)

    Schüller, H; Wisser, L; Pauleit, D

    1997-09-01

    Bone metastases causing pain syndromes and imminent pathologic fractures are among the main reasons for radiotherapy in patients suffering from malignant tumors. The indication is much influenced by the radiologic findings. Surgical methods are to be chosen in the first place in cases of pathologic fractures or patients with a high risk of such fractures. Different authors recommend various therapeutic regimens. Effective pain control can be achieved with one single dose of radiation. Doses of 6 to 40 Gy applied in one to 19 days are also efficient. Side effects, especially nausea and vomiting occur in 25% of cases; this number rises to 50% in cases of half body irradiation. Visible changes of bone mineral density may be noticed about 6 weeks after termination of radiotherapy. About 70% of osteolytic metastases show progressive sclerosis whereas osteosclerotic lesions may show both increase or decline of bone mass. In spite many years of experience the optimal strategy for radiation therapy of bone metastasis has not been defined; further studies are needed.

  17. Subgroups of Castration-resistant Prostate Cancer Bone Metastases Defined Through an Inverse Relationship Between Androgen Receptor Activity and Immune Response.

    Science.gov (United States)

    Ylitalo, Erik Bovinder; Thysell, Elin; Jernberg, Emma; Lundholm, Marie; Crnalic, Sead; Egevad, Lars; Stattin, Pär; Widmark, Anders; Bergh, Anders; Wikström, Pernilla

    2017-05-01

    Novel therapies for men with castration-resistant prostate cancer (CRPC) are needed, particularly for cancers not driven by androgen receptor (AR) activation. To identify molecular subgroups of PC bone metastases of relevance for therapy. Fresh-frozen bone metastasis samples from men with CRPC (n=40), treatment-naïve PC (n=8), or other malignancies (n=12) were characterized using whole-genome expression profiling, multivariate principal component analysis (PCA), and functional enrichment analysis. Expression profiles were verified by reverse transcription-polymerase chain reaction (RT-PCR) in an extended set of bone metastases (n=77) and compared to levels in malignant and adjacent benign prostate tissue from patients with localized disease (n=12). Selected proteins were evaluated using immunohistochemistry. A cohort of PC patients (n=284) diagnosed at transurethral resection with long follow-up was used for prognostic evaluation. The majority of CRPC bone metastases (80%) was defined as AR-driven based on PCA analysis and high expression of the AR, AR co-regulators (FOXA1, HOXB13), and AR-regulated genes (KLK2, KLK3, NKX3.1, STEAP2, TMPRSS2); 20% were non-AR-driven. Functional enrichment analysis indicated high metabolic activity and low immune responses in AR-driven metastases. Accordingly, infiltration of CD3(+) and CD68(+) cells was lower in AR-driven than in non-AR-driven metastases, and tumor cell HLA class I ABC immunoreactivity was inversely correlated with nuclear AR immunoreactivity. RT-PCR analysis showed low MHC class I expression (HLA-A, TAP1, and PSMB9 mRNA) in PC bone metastases compared to benign and malignant prostate tissue and bone metastases of other origins. In primary PC, low HLA class I ABC immunoreactivity was associated with high Gleason score, bone metastasis, and short cancer-specific survival. Limitations include the limited number of patients studied and the single metastasis sample studied per patient. Most CRPC bone metastases show

  18. Radiotherapy for pain management of bone metastases

    Energy Technology Data Exchange (ETDEWEB)

    Rezende Junior, Ismar de; Mattos, Marcos Duarte de; Nakamura, Ricardo; Lemes Junior, Joaquim; Vanzelli, Talita Lozano, E-mail: rezende.med@terra.com.br [Radioterapia do Hospital de Cancer de Barretos, SP (Brazil)

    2011-07-01

    Purpose: This is the first Brazilian study intended to evaluate the response of pain relief with radiotherapy in three different fractionation and the clinical differences in managing pain in patients with painful bone metastases. Methods: Prospective study of patients with painful bone metastases referred to the Radiotherapy Sector of the Hospital de Cancer de Barretos for pain-relieving radiotherapy between March and December 2010. It is known that radiotherapy seems to alter the activation of osteoclast-mediated bone resorption, relieving pain in cases of painful bone metastases. Patients were assessed in relation to the status of pain intensity before and after the initiation of radiotherapy. Either a single fraction of 8Gy, five fractions of 4Gy or ten fractions of 3Gy were given. A visual analog scale (VAS) was applied by doctors, nurses and nursing technicians to assess pain intensity at each session of radiotherapy, and follow-up at 8, 30 and 90 days from the end of treatment. Results: We evaluated 92 consecutive patients, 48 male and 44 female, with a median age of 58 years. We found that 14% of patients referred from the Palliative Care or Clinical Oncology sectors need better pharmacological analgesia due to severe pain, compared with 40.5% of patients from the other sectors (p = 0.004). We also found that the onset of pain relief to patients receiving 10 fractions of 300cGy analgesia without changing the pre-radiotherapy analgesia occurred with significance after the fifth fraction. Improvement in pain experienced within 90 days of follow-up was found in eighty percent of patients, independent of fractionated radiotherapy, site of metastases and the clinical condition of the patient. Discussion/Conclusion: The Palliative Care and Clinical Oncology sectors expressed greater concern in regards to analgesia for the patient with painful bone metastases. Radiotherapy is an effective pain-relieving treatment in different fractionation studied, even though the

  19. Appearance of untreated bone metastases from breast cancer on FDG PET/CT: importance of histologic subtype

    Energy Technology Data Exchange (ETDEWEB)

    Dashevsky, Brittany Z.; Parsons, Molly [Weill Cornell Medical College, Department of Radiology, New York, NY (United States); Goldman, Debra A.; Goenen, Mithat [Memorial Sloan-Kettering Cancer Center, Department of Epidemiology and Biostatistics, New York, NY (United States); Corben, Adriana D. [Memorial Sloan-Kettering Cancer Center, Department of Pathology, New York, NY (United States); Jochelson, Maxine S.; Ulaner, Gary A. [Weill Cornell Medical College, Department of Radiology, New York, NY (United States); Memorial Sloan-Kettering Cancer Center, Department of Radiology, New York, NY (United States); Hudis, Clifford A. [Memorial Sloan-Kettering Cancer Center, Department of Medicine, New York, NY (United States); Morrow, Monica [Memorial Sloan-Kettering Cancer Center, Department of Surgery, New York, NY (United States)

    2015-10-15

    To determine if the histology of a breast malignancy influences the appearance of untreated osseous metastases on FDG PET/CT. This retrospective study was performed under IRB waiver. Our Hospital Information System was screened for breast cancer patients who presented with osseous metastases, who underwent FDG PET/CT prior to systemic therapy or radiotherapy from 2009 to 2012. Patients with invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), or mixed ductal/lobular (MDL) histology were included. Patients with a history of other malignancies were excluded. PET/CT was evaluated, blinded to histology, to classify osseous metastases on a per-patient basis as sclerotic, lytic, mixed lytic/sclerotic, or occult on CT, and to record SUVmax for osseous metastases on PET. Following screening, 95 patients who met the inclusion criteria (74 IDC, 13 ILC, and 8 MDL) were included. ILC osseous metastases were more commonly sclerotic and demonstrated lower SUVmax than IDC metastases. In all IDC and MDL patients with osseous metastases, at least one was FDG-avid. For ILC, all patients with lytic or mixed osseous metastases demonstrated at least one FDG-avid metastasis; however, in only three of seven patients were sclerotic osseous metastases apparent on FDG PET. The histologic subtype of breast cancer affects the appearance of untreated osseous metastases on FDG PET/CT. In particular, non-FDG-avid sclerotic osseous metastases were more common in patients with ILC than in patients with IDC. Breast cancer histology should be considered when interpreting non-FDG-avid sclerotic osseous lesions on PET/CT, which may be more suspicious for metastases (rather than benign lesions) in patients with ILC. (orig.)

  20. Correlation between low Gleason score and prostate specific antigen levels with incidence of bone metastases in prostate cancer patients: when to omit bone scans?

    Science.gov (United States)

    Sanjaya, I Putu Gde; Mochtar, Chaidir Arief; Umbas, Rainy

    2013-01-01

    To identify correlation and incidence of bone metastases in prostate cancer patient with low Gleason scores (GS) and prostate specific antigen (PSA) levels. This descriptive restrospective study covered patients with prostate cancer in Cipto Mangunkusumo Hospital in 2006-2011. Of a total of 478, those who had PSA values, histological examination, and bone scan were included, resulting in 358 eligible cases. PSA values were measured using the sandwich electrochemiluminescent immunoassay. Histological examination was graded according to Gleason's grading system and divided into 3 categories: well differentiated (GS ≤ 6), moderately differentiated (GS 7) and poorly differentiated (GS 8-10). Bone scans were performed using a radiopharmaceutical agent (Tc 99m methylenen diphosphonate) with images captured by gamma camera. The mean age was 67.5 ± 7.8, mean GS was 7.7 ± 1.3 and median PSA was 56.9 (range: 0.48-17000 ng/ mL). There were 11 patients (3.0%) with positive bone scan with PSAbone metastasis. In our study, there were still small percentage of patients with bone metastasis even when low values of PSA (PSA<10 ng/mL) and GS (GS ≤ 6) were applied.

  1. CyberKnife stereotactic radiosurgery and stereotactic ablative radiation therapy of patients with prostate cancer bone metastases.

    Science.gov (United States)

    Napieralska, A; Miszczyk, L; Stapor-Fudzinska, M

    2016-01-01

    The aim of the study was to evaluate the effectiveness and toxicity of CyberKnife (CK) stereotactic radiosurgery (SRS) and stereotactic ablative radiation therapy (SABR) of patients with prostate cancer bone metastases. Analysis of prognostic and predictive factors was also performed. Material consisted of 51 patients with 71 bone oligometastases treated using CK SRS/SABR. In half of the patients single lesion was treated, in half 2-5 lesions. Median PSA concentration at the time of metastasis detection was 5.75 ng/ml. Total dose of 6-45Gy (median 20) was delivered with 1-5 fractions of 6-15 Gy (median 9). Biologic equivalent dose (BED) (α/β=1.6) over 100 Gy was delivered to 45 lesions (63%) in 38 patients (75%). In statistical analysis Kaplan-Meier method, log-rank test and the Cox proportional hazard model were used. One-, two- and three-year overall survival (OS) was 90%, 76% and 70%, respectively. All patients having PSA concentration lower that 1 ng/ml at last control lived at least three years. One-, two- and three- year local control (LC) was 97%, 70% and 30%. Patients with PSA below 20 ng/ml at the time of metastasis detection had better local control of lesions and lower PSA at the last control. Median of PSA concentration after CK based SRS/SABR remains stable during first 12 months of follow-up, dropped during the next months and at last control was comparable to initial level. Median PSA at last control in patients without disease progression was 1.67ng/ml and 20 patients had PSA below 1.0ng/ml. At the last control 59% of patients had no other metastases. Rapid pain decrease was observed in analysed group and during each control about 90% of patients had pain relief. No major toxicity was observed, 3 patients suffered from fracture of irradiated bone.SRS/SABR of prostate cancer bone oligometastases provides good LC of lesions, excellent pain control without additional toxicity. Patients with PSA concentration below 20ng/ml at the time of metastasis

  2. External radiotherapy for bone and lymph-node metastases from thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Niunoya, Koichiro [Omoto Geriatric Health Service' s Facility, Tokyo (Japan); Kusakabe, Kiyoko; Obara, Takao; Ito, Yukio [Tokyo Women' s Medical Coll. (Japan); Fujimoto, Yoshihide [Cancer Inst. Hospital, Tokyo (Japan)

    2002-12-01

    The therapeutic effects of external beam radiation to bone or lymph-node metastatic lesions of thyroid cancer were evaluated in 11 patients. These 11 cases included four male and seven female patients ranging in age from 44 to 69 years (mean age 54 years), were treated by 4MV-Xray irradiation. Thyroid surgery had been performed in all patients. The thyroid tumors were classified histologically as papillary carcinoma in 3 patients and follicular carcinoma in 8. Following surgical total thyroidectomy, thyroid ablation and/or therapy with I-131 was performed in 8 patients with follicular carcinoma. Using a 4MV-Xray external beam, a total dose of 54 to 68 Gy (mean dose 62 Gy) was delivered to 28 metastatic lesions including 2 lymph nodes and 26 bones, although an 82-Gy total dose was used for one lymph node. All patients underwent follow-up for more than 8 years. Ten of the 11 patients died, 6 of thyroid cancer and 4 of other diseases. Two of them suffered anaplastic transformation of differentiated thyroid carcinoma and died. The survival term was 0.2 to 8.6 years (mean 4.9 years) after initial external radiotherapy. Local irradiation with a curative dose was able to control most of the lesions in the 11 patients (29 lesions with the exception of 2 cases showing anaplastic transformation). In some patients, pain relief was obtained although tumor size measured by CT did not reveal marked regression. External beam radiation therapy with a curative dose was thought to be beneficial for patients with metastatic lesions of thyroid cancer as slow-growing and having relatively long survival period of patients. (author)

  3. USE OF ZOLEDRONIC ACID AND A RАNK LIGAND INHIBITOR IN THE PALLIATIVE TREATMENT OF CANCERS OF THE PROSTATE WITH BONE METASTASES

    Directory of Open Access Journals (Sweden)

    S. V. Mushigin

    2013-01-01

    Full Text Available In the metastatic patterns of the cancer, the tumor foci are located more frequently in the tubular bones and vertebral column, just less frequently in the bones of the pelvis, and even more rarely in those of the shoulder and skull. Bone pain is usually related to the involvement of the periosteum that has an extensive network of nociceptors. Auxiliary exposures that directly affect the intensity of pain syndrome and the strength of bone structures are used in addition to basic therapy options for cancer of the prostate. Among these agents there are bisphosphonates. Once ingested, bisphosphonates are transported by blood to the areas of active bone tissue rearrangement where they are tightly bound to the mineral matrix. Their administration causes a considerable reduction in pain syndrome, a decrease in the frequency of complications of bone metastases, and an increase in time before a first bone complication. Antiresorptive therapy including particularly zoledronic acid (resorba or denosumab is a necessary treatment option in the above category of patients with bone metastases.

  4. USE OF ZOLEDRONIC ACID AND A RАNK LIGAND INHIBITOR IN THE PALLIATIVE TREATMENT OF CANCERS OF THE PROSTATE WITH BONE METASTASES

    Directory of Open Access Journals (Sweden)

    S. V. Mushigin

    2014-07-01

    Full Text Available In the metastatic patterns of the cancer, the tumor foci are located more frequently in the tubular bones and vertebral column, just less frequently in the bones of the pelvis, and even more rarely in those of the shoulder and skull. Bone pain is usually related to the involvement of the periosteum that has an extensive network of nociceptors. Auxiliary exposures that directly affect the intensity of pain syndrome and the strength of bone structures are used in addition to basic therapy options for cancer of the prostate. Among these agents there are bisphosphonates. Once ingested, bisphosphonates are transported by blood to the areas of active bone tissue rearrangement where they are tightly bound to the mineral matrix. Their administration causes a considerable reduction in pain syndrome, a decrease in the frequency of complications of bone metastases, and an increase in time before a first bone complication. Antiresorptive therapy including particularly zoledronic acid (resorba or denosumab is a necessary treatment option in the above category of patients with bone metastases.

  5. Spine metastases in prostate cancer: comparison of technetium‐99m‐MDP whole‐body bone scintigraphy, [18F]choline positron emission tomography(PET)/computed tomography (CT) and [18F]NaF PET/CT

    National Research Council Canada - National Science Library

    Poulsen, Mads H; Petersen, Henrik; Høilund‐Carlsen, Poul F; Jakobsen, Jørn S; Gerke, Oke; Karstoft, Jens; Steffansen, Signe I; Walter, Steen

    2014-01-01

    ... (PET)/computed tomography (CT) and [(18) F]-fluoromethylcholine (FCH) PET/CT. The study entry criteria were biopsy-proven prostate cancer, a positive WBS consistent with bone metastases, and no history of androgen deprivation...

  6. Detection of metastases in breast cancer patients. Comparison of FDG PET with chest X-ray, bone scintigraphy and ultrasound of the abdomen

    Energy Technology Data Exchange (ETDEWEB)

    Dose-Schwarz, J.; Mahner, S.; Schirrmacher, S.; Mueller, V. [Klinik und Poliklinik fuer Gynaekologie, Universitaetsklinikum Hamburg-Eppendorf (Germany); Jenicke, L.; Brenner, W. [Klinik fuer Nuklearmedizin, Universitaetsklinikum Hamburg-Eppendorf (Germany); Habermann, C.R. [Klinik fuer Diagnostische und Interventionelle Radiologie, Universitaetsklinikum Hamburg-Eppendorf (Germany)

    2008-07-01

    Distant metastases at primary diagnosis are a prognostic key factor in breast cancer patients and play a central role in therapeutic decisions. To detect them, chest X-ray, abdominal ultrasound, and bone scintigraphy are performed as standard of care in Germany and many centers worldwide. Although FDG PET detects metastatic disease with high accuracy, its diagnostic value in breast cancer still needs to be defined. The aim of this study was to compare the diagnostic performance of FDG PET with conventional imaging. Patients, methods: a retrospective analysis of 119 breast cancer patients who presented for staging was performed. Whole-body FDG-PET (n = 119) was compared with chest X-ray (n = 106) and bone scintigraphy (n = 95). Each imaging modality was independently assessed and classified for metastasis (negative, equivocal and positive). The results of abdominal ultrasound (n = 100) were classified as negative and positive according to written reports. Imaging results were compared with clinical follow-up including follow-up imaging procedures and histopathology. Results: FDG-PET detected distant metastases with a sensitivity of 87.3% and a specificity of 83.3%. In contrast, the sensitivity and specificity of combined conventional imaging procedures was 43.1% and 98.5%, respectively. Regarding so-called equivocal and positive results as positive, the sensitivity and specificity of FDG-PET was 93.1% and 76.6%, respectively, compared to 61.2% and 86.6% for conventional imaging. Regarding different locations of metastases the sensitivity of FDG PET was superior in the detection of pulmonary metastases and lymph node metastases of the mediastinum in comparison to chest X-ray, whereas the sensitivity of FDG PET in the detection of bone and liver metastases was comparable with bone scintigraphy and ultrasound of the abdomen. Conclusions: FDG-PET is more sensitive than conventional imaging procedures for detection of distant breast cancer metastases and should be

  7. Multimodal imaging of bone metastases: From preclinical to clinical applications

    Directory of Open Access Journals (Sweden)

    Stephan Ellmann

    2015-10-01

    Full Text Available Metastases to the skeletal system are commonly observed in cancer patients, highly affecting the patients' quality of life. Imaging plays a major role in detection, follow-up, and molecular characterisation of metastatic disease. Thus, imaging techniques have been optimised and combined in a multimodal and multiparametric manner for assessment of complementary aspects in osseous metastases. This review summarises both application of the most relevant imaging techniques for bone metastasis in preclinical models and the clinical setting.

  8. Prostate cancer in patients from rural and suburban areas--PSA value, Gleason score and presence of metastases in bone scan.

    Science.gov (United States)

    Szot, Wojciech; Kostkiewicz, Magdalena; Zając, Joanna; Owoc, Alfred; Bojar, Iwona

    2014-01-01

    Prostate cancer is the second most common neoplasm among men both worldwide and in Poland. In prostate cancer, bone metastasis is related to a poorer prognosis. A diagnosis of metastatic bone disease is important in prostate cancer patients prior to therapy. Prostate specific antigen (PSA) serum value is used both as a screening tool and for staging of prostate cancer. To evaluate whether there is a link between symptoms presented by patients, pain in particular, and the presence, number and location of bone metastases as assessed by bone scan scintigraphy in concordance with PSA values and Gleason scores. A group of 186 patients (aged: 68.38±6.16) diagnosed with prostate cancer, from rural and suburban areas of Małopolska province, that was directed for bone scan scintigraphy to the Nuclear Medicine Dept, John Paul II Hospital in Kraków. Analysis of all laboratory findings (including PSA value) and a biopsy were performed. Then, bone scan scintigraphy was done with the use of methylene disphosphonate (MDP) labeled with Tc-99m. In patients with a Gleason value≤7 and a PSA value≤20 ng/ml, the cutoff value for a negative bone scan with a confidence interval of 0.95 was established at a PSA value below 10 ng/ml (pbone scan (r=0.45, p=0.05), the number of metastases (r=0.66, pbone scan scintigraphy in prostate cancer staging. The cutoff value for negative bone scan with a 95% confidence interval was established at PSA=10 ng/ml.

  9. Combined use of zoledronic acid and 153Sm-EDTMP in hormone-refractory prostate cancer patients with bone metastases

    Energy Technology Data Exchange (ETDEWEB)

    Lam, Marnix G.E.H.; Rijk, Peter P. van [University Medical Center Utrecht, Department of Nuclear Medicine, P.O. Box 85500, Utrecht (Netherlands); Dahmane, Amel; Stevens, Wil H.M. [CIS bio International, Saclay (France); Klerk, John M.H. de [Meander Medical Center, Department of Nuclear Medicine, Amersfoort (Netherlands); Zonnenberg, Bernard A. [UMC Utrecht, Department of Internal Medicine, Utrecht (Netherlands)

    2008-04-15

    {sup 153}Sm-ethylenediaminetetramethylenephosphonic acid (EDTMP; Quadramet {sup registered}) is indicated for the treatment of painful bone metastases, whereas zoledronic acid (Zometa {sup registered}) is indicated for the prevention of skeletal complications. Because of the different therapeutic effects, combining the treatments may be beneficial. Both, however, accumulate in areas with increased osteoblastic activity. Possible drug interactions were investigated. Patients with hormone-refractory prostate cancer were treated with 18.5 MBq/kg {sup 153}Sm-EDTMP in weeks 1 and 3 and with 37 MBq/kg in week 15. Treatment with 4 mg zoledronic acid began in week 3 and continued every 4 weeks through week 23. In weeks 3 and 15, zoledronic acid was administered 2 days before {sup 153}Sm-EDTMP treatment. Urine was collected 48 h after injection of {sup 153}Sm-EDTMP, and whole-body images were obtained 6, 24 and 48 h post-injection. The effect of zoledronic acid on total bone uptake of {sup 153}Sm-EDTMP was measured indirectly by the cumulative activity excreted in the urine in weeks 1, 3 and 15. Biodistribution, safety, tolerability and effect on prostate-specific antigen level were also studied. The urinary excretion in week 3 divided by the urinary excretion in week 1 (baseline) times 100% was mean 98.4 {+-} 11.6% (median 96.2%). From week 1 to 15, after four zoledronic acid treatments, the mean ratio was 101.9 {+-} 10.7% (median 101.8%). Bioequivalence could be concluded by using a two-sample t test for both per-protocol (n = 13) and full-analysis sets (n = 18). Toxicity was comparable to of monotherapy with {sup 153}Sm-EDTMP. Zoledronic acid treatment does not influence {sup 153}Sm-EDTMP skeletal uptake. Combined treatment is feasible and safe. (orig.)

  10. Enhancing Quality of Life for Breast Cancer Patients with Bone Metastases

    Science.gov (United States)

    2008-04-01

    tumor-induced osteolysis provides an ethical and cost-effective way to evaluate the effect of therapy on the progression of osteolysis. Serial...hormone increases bone formation in adult rats by activation of bone lining cells. Endocrinology 136:3632-8; 1995. 26. Elte , J. W., Bijvoet, O. L

  11. Can surgical management of bone metastases improve quality of life among women with gynecologic cancer?

    National Research Council Canada - National Science Library

    Ji, Tao; Eskander, Ramez; Wang, Yifei; Sun, Kunkun; Hoang, Bang H; Guo, Wei

    2014-01-01

    .... In order to critically evaluate the role of surgery, we retrospectively analyzed the records of 18 patients surgically treated for metastatic gynecologic tumors of bone, focusing on quality of life...

  12. Design of polyaspartic acid peptide-poly (ethylene glycol)-poly (ε-caprolactone) nanoparticles as a carrier of hydrophobic drugs targeting cancer metastasized to bone.

    Science.gov (United States)

    Liu, Jinsong; Zeng, Youyun; Shi, Shuai; Xu, Lihua; Zhang, Hualin; Pathak, Janak L; Pan, Yihuai

    2017-01-01

    Treatment of cancer metastasized to bone is still a challenge due to hydrophobicity, instability, and lack of target specificity of anticancer drugs. Poly (ethylene glycol)-poly (ε-caprolactone) polymer (PEG-PCL) is an effective, biodegradable, and biocompatible hydrophobic drug carrier, but lacks bone specificity. Polyaspartic acid with eight peptide sequences, that is, (Asp)8, has a strong affinity to bone surface. The aim of this study was to synthesize (Asp)8-PEG-PCL nanoparticles as a bone-specific carrier of hydrophobic drugs to treat cancer metastasized to bone. 1H nuclear magnetic resonance, Fourier transform infrared spectroscopy, and transmission electron microscopy data showed that (Asp)8-PEG-PCL nanoparticles (size 100 nm) were synthesized successfully. (Asp)8-PEG-PCL nanoparticles did not promote erythrocyte aggregation. Fluorescence microscopy showed clear uptake of Nile red-loaded (Asp)8-PEG-PCL nanoparticles by cancer cells. (Asp)8-PEG-PCL nanoparticles did not show cytotoxic effect on MG63 and human umbilical vein endothelial cells at the concentration of 10-800 μg/mL. (Asp)8-PEG-PCL nanoparticles bound with hydroxyapatite 2-fold more than PEG-PCL. Intravenously injected (Asp)8-PEG-PCL nanoparticles accumulated 2.7-fold more on mice tibial bone, in comparison to PEG-PCL. Curcumin is a hydrophobic anticancer drug with bone anabolic properties. Curcumin was loaded in the (Asp)8-PEG-PCL. (Asp)8-PEG-PCL showed 11.07% loading capacity and 95.91% encapsulation efficiency of curcumin. The curcumin-loaded (Asp)8-PEG-PCL nanoparticles gave sustained release of curcumin in high dose for >8 days. The curcumin-loaded (Asp)8-PEG-PCL nanoparticles showed strong antitumorigenic effect on MG63, MCF7, and HeLa cancer cells. In conclusion, (Asp)8-PEG-PCL nanoparticles were biocompatible, permeable in cells, a potent carrier, and an efficient releaser of hydrophobic anticancer drug and were bone specific. The curcumin-loaded (Asp)8-PEG-PCL nanoparticles showed

  13. A meta-analysis of {sup 18}FDG-PET, MRI and bone scintigraphy for diagnosis of bone metastases in patients with breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Tao; Yang, Hui-Lin [The First Affiliated Hospital of Soochow University, Department of Orthopaedic Surgery, Suzhou (China); Cheng, Tao [Shanghai Jiaotong University School of Medicine, Department of Orthopaedic Surgery, Shanghai Sixth People' s Hospital, Shanghai (China); Xu, Wen [Public Health School of Soochow University, Department of Epidemiology and Biostatistics, Suzhou (China); Yan, Wei-Li [Shanghai Jiaotong University School of Medicine, Departments of Nuclear Medicine, Shanghai Renji Hospital, Shanghai (China); Liu, Jia [Shanghai Jiaotong University School of Medicine, Departments of Radiology, Shanghai Renji Hospital, Shanghai (China)

    2011-05-15

    To perform a meta-analysis comparing the diagnostic value of {sup 18}FDG-PET, MRI, and bone scintigraphy (BS) in detecting bone metastases in patients with breast cancer. MEDLINE, EMBASE, Scopus, ScienceDirect, SpringerLink, Web of Knowledge, EBSCO, and the Cochrane Database of Systematic Review databases were searched for relevant original articles published from January 1995 to January 2010. Inclusion criteria was as follows: {sup 18}FDG-PET, MRI or {sup 99m}Tc-MDP BS was performed to detect bone metastases (the number of published CT studies was inadequate for meta-analysis and therefore could not be included in this study); sufficient data were presented to construct a 2 x 2 contingency table; histopathological analysis and/or close clinical and imaging follow-up for at least 6 months were used as the reference standard. Two reviewers independently assessed potentially eligible studies and extracted relevant data. A software program called ''META-DiSc'' was used to obtain the pooled estimates for sensitivity, specificity, diagnostic odds ratio (DOR), summary receiver operating characteristic (SROC) curves, and the *Q index for each modality. Thirteen articles consisting of 23 studies fulfilled all inclusion criteria. On a per-patient basis, the pooled sensitivity estimates for MRI (97.1%) were significantly higher than those for PET (83.3%) and BS (87.0%; P <0.05). There was no significant difference between PET and BS (P <0.05). The pooled specificity estimates for PET (94.5%) and MRI (97.0%) were both significantly higher than those for BS (88.1%; P <0.05). There was no significant difference between PET and MRI (P >0.05). The pooled DOR estimates for MRI (298.5) were significantly higher than those for PET (82.1%) and BS (49.3%; P <0.05). There was no significant difference between PET and BS (P >0.05). The SROC curve for MRI showed better diagnostic accuracy than those for PET and BS. The SROC curve for PET was better than that for BS

  14. [Surgical treatment of spinal bone metastases].

    Science.gov (United States)

    Saqui, Abderrazzak El; Aggouri, Mohamed; Benzagmout, Mohamed; Chakour, Khalid; Chaoui, Mohamed El Faiz

    2017-01-01

    Surgery for metastatic tumor is usually a palliative surgery, especially for spinal metastases, due to their anatomical localization. Surgical procedure should be accurately established to have simple outcomes and to start adjuvant treatment as soon as clinically possible. Therapeutic strategy should proceed after multidisciplinary consultation meeting (RCP). The main risk of spinal bone metastases is neurological, hence this surgery should be most commonly preventive. Its main objective is to improve patient's quality of life.

  15. Validity of the recorded International Classification of Diseases, 10th edition diagnoses codes of bone metastases and skeletal-related events in breast and prostate cancer patients in the Danish National Registry of Patients

    Directory of Open Access Journals (Sweden)

    Annette Østergaard Jensen

    2009-07-01

    Full Text Available Annette Østergaard Jensen1, Mette Nørgaard1, Mellissa Yong2, Jon P Fryzek2, Henrik Toft Sørensen11Department of Clinical Epidemiology, Aarhus University hospital, Århus, Denmark; 2Global Epidemiology, Amgen inc., Thousands Oaks, CA, USAObjective: The clinical history of bone metastases and skeletal-related events (SREs secondary to cancers is not well understood. In support of studies of the natural history of bone metastases and SREs in Danish prostate and breast cancer patients, we estimated the sensitivity and specificity of hospital diagnoses for bone metastases and SREs (ie, radiation therapy to the bone, pathological or osteoporotic fractures, spinal cord compression and surgery to the bone in a nationwide medical registry in Denmark.Study design and setting: In North Jutland County, Denmark, we randomly sampled 100 patients with primary prostate cancer and 100 patients with primary breast cancer diagnoses from the National Registry of Patients (NRP, during the period January 1st, 2000 to December 31st, 2000 and followed them for up to five years after their cancer diagnosis. We used information from medical chart reviews as the reference for estimating sensitivity, and specificity of the NRP International Classification of Diseases, 10th edition (ICD-10 coding for bone metastases and SRE diagnoses. Results: For prostate cancer, the overall sensitivity of bone metastases or SRE coding in the NRP was 0.54 (95% confidence interval [CI]: 0.39–0.69, and the specificity was 0.96 (95% CI: 0.87–1.00. For breast cancer, the overall sensitivity of bone metastases or SRE coding in the NRP was 0.58 (95% CI: 0.34–0.80, and the specificity was 0.95 (95% CI: 0.88–0.99. Conclusion: We measured the validity of ICD-10 coding in the Danish NRP for bone metastases and SREs in prostate and breast cancer patients and found it has adequate sensitivity and high specificity. The NRP remains a valuable tool for clinical epidemiological studies of bone

  16. Computed tomography-guided percutaneous microwave ablation combined with osteoplasty for palliative treatment of painful extraspinal bone metastases from lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Wei, Zhigang; Ye, Xin; Yang, Xia; Zheng, Aimin; Huang, Guanghui; Wang, Jiao [Shandong Provincial Hospital Affiliated to Shandong University, Department of Oncology, Jinan, Shandong Province (China); Zhang, Kaixian [Teng Zhou Central People' s Hospital Affiliated to Jining Medical College, Department of Oncology, Tengzhou, Shandong Province (China)

    2015-10-15

    To retrospectively evaluate the efficacy and safety of microwave ablation (MWA) combined with osteoplasty in lung cancer patients with painful extraspinal bone metastases. From January 2011 to July 2014, 26 lung cancer patients with 33 painful extraspinal bone metastases underwent percutaneous MWA combined with osteoplasty. Effectiveness was evaluated by visual analog scale (VAS) and daily morphine dose with a follow-up of 6-months. Complications were also recorded. Mean VAS score and morphine dose pre-procedure were 7.4 ± 1.6 (range, 5-10) and 47.7 ± 30.1 mg (range, 20-120 mg), respectively. Technical success and pain relief were achieved in all patients. Mean VAS scores and daily morphine doses post-procedure were as follows: 48 h, 1.7 ± 1.2 (p < 0.001) and 29.6 ± 16.1 mg (p = 0.003); 7 days, 1.9 ± 1.7 (p < 0.001) and 16.1 ± 12.0 mg (p < 0.001); 1 month, 1.5 ± 0.9 (p < 0.001) and 10.8 ± 10.9 (p < 0.001); 3 months, 0.9 ± 0.7 (p < 0.001) and 8.4 ± 9.2 mg (p < 0.001); and 6 months, 1.2 ± 0.8 (p < 0.001) and 9.2 ± 12.3 mg (p < 0.001). Complications were observed in eight patients (28 %); among these, major complications were reported in two (7.7 %) patients, one with local infection and the other with a bone fracture. The minor complication rate was 23.1 % (6/26). MWA combination with osteoplasty appeared to be an effective and safe treatment for lung cancer patients with painful extraspinal bone metastases. (orig.)

  17. Brain metastasization of breast cancer.

    Science.gov (United States)

    Custódio-Santos, Tânia; Videira, Mafalda; Brito, Maria Alexandra

    2017-08-01

    Central nervous system metastases have been reported in 15-25% of breast cancer patients, and the incidence is increasing. Moreover, the survival of these patients is generally poor, with reports of a 1-year survival rate of 20%. Therefore, a better knowledge about the determinants of brain metastasization is essential for the improvement of the clinical outcomes. Here, we summarize the current data about the metastatic cascade, ranging from the output of cancer cells from the primary tumour to their colonization in the brain, which involves the epithelial-mesenchymal transition, invasion of mammary tissue, intravasation into circulation, and homing into and extravasation towards the brain. The phenotypic change in malignant cells, and the importance of the microenvironment in the formation of brain metastases are also inspected. Finally, the importance of genetic and epigenetic changes, and the recently disclosed effects of microRNAs in brain metastasization of breast cancer are highlighted. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Musculoskeletal Complications and Bone Metastases in Breast Cancer PatientsUndergoing Estrogen Deprivation Therapy

    Science.gov (United States)

    2016-10-01

    Francisco, CA 07/31/11 The American Society of Pharmacognosy Annual Meeting, Mechanism of Action Series, San Diego, CA 03/07, 11/08, 11/10...Research Conference on Complementary & Integrative Medicine Trainee Travel Award recipient, Minneapolis, MN 2009 American Society of Pharmacognosy Student...Differential effects of medicinal Zingiberaceae on the prevention of bone loss. American Society of Pharmacognosy Annual Meeting, Honolulu, HI, June

  19. Bone Cancer

    Science.gov (United States)

    Cancer that starts in a bone is uncommon. Cancer that has spread to the bone from another ... more common. There are three types of bone cancer: Osteosarcoma - occurs most often between ages 10 and ...

  20. 18F-Fluorodeoxyglucose-positron Emission Tomography/Computed Tomography Imaging of Metastatic Nasopharyngeal Cancer with Emphasis on the Distribution of Bone Metastases

    Science.gov (United States)

    Al Tamimi, Ammad Shanoon; Zaheer, Sumbul; Ng, David Chee; Osmany, Saabry

    2017-01-01

    Distant metastases change the prognosis of patients with nasopharyngeal carcinoma (NPC) which most commonly metastasizes to the bone. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) is reported as useful in imaging NPC metastases. Our study assesses the incidence and distribution of bone metastases detected by 18F-FDG PET/CT in NPC. 717 18F-FDG PET/CT scan reports of histologically proven NPC patients imaged in Singapore General Hospital, Singapore, between 2003 and 2009 were reviewed for the total number of metastases (scanned from vertex to mid-thigh) and analyzed for distribution. Of the 709 FDG avid metastases in these reports, 357/709 (50.35%) were locoregional nodal metastasis and 352/709 (49.65%) were distant metastases of which 192/709 (27.08%) of total metastases and 54.54% of distant metastases (192/352) were in the bones. The majority of the bone lesions 125/192 (65.1%) were in the axial skeleton with 109/192 (56.77%) in the lower skeleton (thoracolumbar spine, sacrum, and pelvis). The incidence of bone metastases in our study (27.08%) was higher than that reported in other studies, for example, 15% by Liu et al. and 11% (230 patients) by Caglar et al. Bone metastases have been reported in the femurs and the feet and as such some metastases may have been outside the field of view of the scans. In our study, 27% of FDG avid NPC metastases are in the bones. PMID:28670176

  1. [Lymph node and distant metastases of thyroid gland cancer. Metastases in the thyroid glands].

    Science.gov (United States)

    Schmid, K W

    2015-11-01

    The different biological features of the various major entities of thyroid cancer, e.g. papillary, follicular, poorly differentiated, anaplastic and medullary, depend to a large extent on their different metastatic spread. Papillary thyroid cancer (PTC) has a propensity for cervical lymphatic spread that occurs in 20-50 % of patients whereas distant metastasis occurs in thyroid cancer (FTC) has a marked propensity for vascular but not lymphatic invasion and 10-20 % of FTC develop distant metastases. At the time of diagnosis approximately one third of medullary thyroid cancer (MTC) cases show lymph node metastases, in 10-15 % distant metastases and 25 % develop metastases during the course of the disease. Poorly differentiated (PDTC) and anaplastic thyroid cancer (ATC) spread via both lymphatic and vascular invasion. Thus distant metastases are relatively uncommon in DTC and when they occur, long-term stable disease is the typical clinical course. The major sites of distant metastases are the lungs and bone. Metastases to the brain, breasts, liver, kidneys, muscle and skin are relatively rare or even rare. The thyroid gland itself can be a site of metastases from a variety of other tumors. In autopsy series of patients with disseminated cancer disease, metastases to the thyroid gland were found in up to 10 % of cases. Metastases from other primary tumors to the thyroid gland have been reported in 1.4-3 % of patients who have surgery for suspected cancer of the thyroid gland. The most common primary cancers that metastasize to the thyroid gland are renal cell (48.1 %), colorectal (10.4 %), lung (8.3 %) and breast cancer (7.8 %) and surprisingly often sarcomas (4.0 %).

  2. [Bone metastases : New aspects of pathogenesis and systemic therapy].

    Science.gov (United States)

    Rachner, T D; Jakob, F; Hofbauer, L C

    2016-07-01

    The occurrence of bone metastases, in particular secondary to breast and prostate cancer, represents a complex medical condition that is debilitating for affected patients. In order to provide an efficient and personalized therapy, an interdisciplinary treatment approach is mandatory; therefore, systemic pharmacological therapy represents a core element of the overall treatment concept. In terms of pathophysiology, the cancer cells cause a massive disturbance of the local bone microenvironment, which as a rule leads to activation of bone resorbing osteoclasts. In addition to bisphosphonates, which can be considered classical antiresorptive agents, the monoclonal receptor activator of nuclear factor-kappa B ligand (RANKL) antibody denosumab has been in use in clinical practice since 2011. The alpha-emitting radioisotope Alpharadin was also recently approved for the treatment of metastatic prostate cancer. This article provides a summary of the most recent knowledge on the pathogenesis of how cancer cells alter the bone microenvironment as well as a review of established and future systemic treatment options.

  3. Pharmacologically Inactive Bisphosphonates as an Alternative Strategy for Targeting Osteoclasts: In Vivo Assessment of 5-Fluorodeoxyuridine-Alendronate in a Preclinical Model of Breast Cancer Bone Metastases.

    Science.gov (United States)

    Schem, Christian; Tower, Robert J; Kneissl, Philipp; Rambow, Anna-Christina; Campbell, Graeme M; Desel, Christine; Damm, Timo; Heilmann, Thorsten; Fuchs, Sabine; Zuhayra, Maaz; Trauzold, Anna; Glüer, Claus C; Schott, Sarah; Tiwari, Sanjay

    2017-03-01

    Bisphosphonates have effects that are antiresorptive, antitumor, and antiapoptotic to osteoblasts and osteocytes, but an effective means of eliciting these multiple activities in the treatment of bone metastases has not been identified. Antimetabolite-bisphosphonate conjugates have potential for improved performance as a class of bone-specific antineoplastic drugs. The primary objective of the study was to determine whether an antimetabolite-bisphosphonate conjugate will preserve bone formation concomitant with antiresorptive and antitumor activity. 5-FdU-ale, a highly stable conjugate between the antimetabolite 5-fluoro-2'-deoxyuridine and the bisphosphonate alendronate, was tested for its therapeutic efficacy in a mouse model of MDA-MB231 breast cancer bone metastases. In vitro testing revealed osteoclasts to be highly sensitive to 5-FdU-ale. In contrast, osteoblasts had significantly reduced sensitivity. Tumor cells were resistant in vitro but in vivo tumor burden was nevertheless significantly reduced compared with untreated mice. Sensitivity to 5-FdU-ale was not mediated through inhibition of farnesyl diphosphate synthase activity, but cell cycle arrest was observed. Although serum tartrate-resistant acid phosphatase (TRAP) levels were greatly reduced by both drugs, there was no significant decrease in the serum bone formation marker osteocalcin with 5-FdU-ale treatment. In contrast, there was more than a fivefold decrease in serum osteocalcin levels with alendronate treatment (p < 0.001). This finding is supported by time-lapse micro-computed tomography analyses, which revealed bone formation volume to be on average 1.6-fold higher with 5-FdU-ale treatment compared with alendronate (p < 0.001). We conclude that 5-FdU-ale, which is a poor prenylation inhibitor but maintains potent antiresorptive activity, does not reduce bone formation and has cytostatic antitumor efficacy. These results document that conjugation of an antimetabolite with

  4. Radium-223 dichloride therapy in breast cancer with osseous metastases.

    Science.gov (United States)

    Takalkar, Amol; Paryani, Bhavna; Adams, Scott; Subbiah, Vivek

    2015-11-18

    Osseous metastases occur frequently in patients with breast cancer. Few options exist for bone targeted therapy for hormone refractory patients with breast cancer with progressive bone metastases. We present a case of breast cancer with osseous metastases but no visceral metastases. The patient had been treated with surgery, chemotherapy, radiation and hormonal therapy, but still had extensive symptomatic osseous metastases. She received radium-223 dichloride, a therapeutic radiopharmaceutical Food and Drug Administration (FDA) approved for castration resistant prostate cancer with bone metastases. She tolerated the therapy well with no significant adverse effects. She had an excellent response with significant pain relief obviating need for regular analgaesics. Her tumour markers also dropped significantly. Osseous metastases assessed with F-18 fluorodeoxy glucose (FDG) positron emission tomography/CT (PET/CT) and F-18 sodium fluoride (NaF) bone PET/CT) scans at baseline, after two and six cycles, also showed interval improvement in the lesions. Radium-223 dichloride could potentially be a safe and useful therapeutic option in this setting. 2015 BMJ Publishing Group Ltd.

  5. Single photon emission computed tomography (SPECT) and SPECT/low-dose computerized tomography did not increase sensitivity or specificity compared to planar bone scintigraphy for detection of bone metastases in advanced breast cancer.

    Science.gov (United States)

    Haraldsen, Ate; Bluhme, Henrik; Røhl, Lisbeth; Pedersen, Erik Morre; Jensen, Anders Bonde; Hansen, Eva Boysen; Nellemann, Hanne; Rasmussen, Finn; Morsing, Anni

    2016-01-01

    To evaluate and compare the diagnostic performance of whole-body planar bone scintigraphy (WBS), single photon emission computed tomography (SPECT), SPECT/low-dose computerized tomography (SPECT/ldCT) and SPECT/contrast enhanced diagnostic CT (SPECT/cdCT) in the staging of patients with advanced breast cancer. Seventy-eight patients with recurrence of biopsy-proven breast cancer and suspicion of disseminated disease were investigated with WBS, SPECT, SPECT/ldCT, SPECT/cdCT and MRI performed on the same day in this prospective study. Images were separately analysed in a blinded fashion by radiologists and nuclear medicine physicians regarding the presence of pathological findings. MRI served as reference standard. According to reference standard, 38 of 73 patients had bone metastases. The sensitivity was 87%, 87%, 79%, and 84% and specificity 63%, 71%, 63% and 83% for WBS, SPECT, SPECT/ldCT and SPECT/cdCT. A significantly increased specificity of SPECT/cdCT compared to WBS and SPECT/ldCT was found, and other parameters did not differ significantly between modalities. Additional two patients had bone metastases solely located outside the MRI scan field and seven patients had soft tissue metastases, but no skeletal changes on MRI. WBS, SPECT and SPECT/ldCT were less sensitive than MRI and equally specific for the detection of bone metastases in patients with advanced breast cancer. Based on our findings, we suggest that initial staging include WBS, MRI of the spine and CT for soft tissue evaluation. Further studies may clarify the potential benefits of whole-body MRI and 18F-NaF PET/CT or 18F-FDG PET/CT. © 2014 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

  6. Disseminated bone metastases from occult thyroid cancer effectively treated with debulking surgery and a single dosimetry-guided administration of radioiodine.

    Science.gov (United States)

    Borsò, Elisa; Boni, Giuseppe; Mazzarri, Sara; Cocciaro, Ardico; Gambacciani, Carlo; Traino, Antonio C; Manca, Giampiero; Grosso, Mariano; Scatena, Cristian; Ortenzi, Valerio; Vannozzi, Riccardo; Marzola, Maria Cristina; Rubello, Domenico; Mariani, Giuliano

    2015-01-01

    In this paper we report on a successful management of multiple bone metastases from differentiated thyroid cancer. In 2007, a 75-year-old female patient, previously referred for thyroidectomy for multinodular goiter, underwent surgical removal of a lumbar mass with histological findings of metastasis from well differentiated thyroid cancer. After surgery, serum thyroglobulin (sTg) was 204.4 ng/mL. A diagnostic/dosimetric (123)I WBS was performed, following stimulation by rTSH. Serial WBSs were acquired, along with SPECT/CT and bone scan for localization of lesions. sTg raised to 3.810 ng/mL, and (123)I WBS showed thyroid remnants and numerous areas with high iodine-uptake corresponding to skeletal sites, the two largest loading on the skull, with osteolytic pattern. Calculated radiation absorbed dose for skull lesions, determined by mean of MIRD methodology, was 63.5 mGy/MBq. The patient underwent surgical removal of the two major skull lesions. Successively, 100 mCi (131)I was administered after stimulation by rTSH, with stimulated sTg 297 ng/mL. After 8 months, diagnostic WBS was negative both for remnants and metastases and rTSH-stimulated Tg was 0.6 ng/mL. To date, the patient has maintained sTg values <1 ng/mL during L-T4 suppressive therapy and after rTSH stimulations. In this unusual case of extensive bone cancerous involvement with high iodine avidity, a multidisciplinary approach based on surgery and dosimetry-guided radiometabolic therapy allowed to accurately assess the patient, execute a small number of treatments and achieve a complete remission of the disease in a very short time, with no additive morbidity. Copyright © 2014 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

  7. Understanding the Progression of Bone Metastases to Identify Novel Therapeutic Targets

    Directory of Open Access Journals (Sweden)

    Annie Schmid-Alliana

    2018-01-01

    Full Text Available Bone is one of the most preferential target site for cancer metastases, particularly for prostate, breast, kidney, lung and thyroid primary tumours. Indeed, numerous chemical signals and growth factors produced by the bone microenvironment constitute factors promoting cancer cell invasion and aggression. After reviewing the different theories proposed to provide mechanism for metastatic progression, we report on the gene expression profile of bone-seeking cancer cells. We also discuss the cross-talk between the bone microenvironment and invading cells, which impacts on the tumour actions on surrounding bone tissue. Lastly, we detail therapies for bone metastases. Due to poor prognosis for patients, the strategies mainly aim at reducing the impact of skeletal-related events on patients’ quality of life. However, recent advances have led to a better understanding of molecular mechanisms underlying bone metastases progression, and therefore of novel therapeutic targets.

  8. Metastasic bone pain management with radioactive isotopes

    OpenAIRE

    Juan Coya Viña

    2005-01-01

    Pain is the commonest clinical manifestation of bone metastases. Its treatment is palliative in nature, and consists of chemotherapy, radiotherapy, hormonotherapy, diphosphonates, and drug therapy (i. e., opiates). Radioactive isotopes represent an appealing alternative to conventional treatment modalities. Among the different types of isotopes, wide clinical experience with 153Sm has been obtained in this laboratory. In the present study, 94 patients (mean age = 65 years), who had been diagn...

  9. Rapid bone repair in a patient with lung cancer metastases to the spine using a novel herbal medicine: A case report.

    Science.gov (United States)

    Pu, Rong; Zhao, Qianhong; Li, Zhimei; Zhang, Lingyan; Luo, Xiaolu; Zeren, Yangji; Yu, Cui; Li, Xianyong

    2016-09-01

    The prognosis of lung carcinoma with metastasis to the bone, particularly to the spine, is poor. Chemotherapy and radiotherapy are established treatments for metastatic bone disease, but their effectiveness is unsatisfactory and bone repair following their use is slow and difficult. Medicine prepared from herbal extracts may be an alternative treatment option. The present study discusses the case of a 59-year-old patient diagnosed with squamous cell lung cancer (T2N3M1) in which first-line chemotherapy using docetaxel plus cisplatin failed. Heavy multiple bone metastases were detected in the T9 vertebra and sixth left rib, resulting in a high risk of pathological fracture. Eastern Cooperative Oncology Group (ECOG) and numerical rating scale (NRS) scores of pain were 2 and 4, respectively. A second-line treatment was chosen consisting of biological intracontrol treatment (BICT) plus bisphosphonates administered over 40 days. BICT is a therapy involving the use of herbal extracts (including ginseng, herba agrimoniae, hairyvein agrimonia herb, white flower patrinia herb and arginine) and palliative care. A partial positive response was reached following use of this regimen, particularly with regard to bone repair. A computed tomography scan revealed a 90% reduction in the broken area of the rib cage and T9 vertebra. The bone repair was rapid and almost complete. In addition, growth of the primary tumor in the right pulmonary hilar and metastasis in the mediastinal lymph nodes were stabilized following treatment. ECOG and NRS scores were decreased to 1 and 0, respectively, leading to an improved quality of life. Based on these results, the present study suggests that this herbal medicine-based regimen promotes bone repair and inhibits tumor growth, with low toxicity. However, the mechanism by which herbal medicine promotes rapid bone repair is unclear. Further studies are required to determine whether cells in the tumor microenvironment are stimulated to undergo re

  10. Combination of icotinib, surgery, and internal-radiotherapy of a patient with lung cancer severely metastasized to the vertebrae bones with EGFR mutation: a case report

    Directory of Open Access Journals (Sweden)

    Qu LL

    2015-06-01

    Full Text Available Li-Li Qu, Hai-Feng Qin, Hong-Jun Gao, Xiao-Qing Liu Department of Lung Cancer, Affiliated Hospital of Academy of Military Medical Science, Beijing, People’s Republic of China Abstract: A 48-year-old Chinese female was referred to us regarding EGFR-mutated advanced non-small cell lung cancer, and metastasis to left scapula and vertebrae bones which caused pathological fracture at T8 and T10 thoracic vertebrae. An aggressive combined therapy with icotinib, vertebrae operation, and radioactive particle implantation and immunotherapy was proposed to prevent paraplegia, relieve pain, and control the overall and local tumor lesions. No postoperative symptoms were seen after surgery, and the pain was significantly relieved. Icotinib merited a 31-month partial response with grade 1 diarrhea as its drug-related adverse event. High dose of icotinib was administered after pelvis lesion progression for 3 months with good tolerance. Combination therapy of icotinib, surgery, and internal radiation for metastases of the vertebrae bones from non-small cell lung cancer seems to be a very promising technique both for sufficient pain relief and for local control of the tumor, vertebrae operation can be an encouraging option for patients with EFGR positive mutation and good prognosis indicator. Keywords: lung cancer, spinal metastasis, pathological fracture, spinal canal stenosis, icotinib

  11. The surgical treatment of pelvic bone metastases.

    Science.gov (United States)

    Müller, Daniel A; Capanna, Rodolfo

    2015-01-01

    Pelvic bone metastases are a growing concern in the field of orthopedic surgery. Patients with pelvic metastasis are individually different with different needs of treatment in order to attain the best possible quality of life despite the advanced stage of disease. A holistic collaboration among the oncologist, radiation therapist, and orthopedic surgeon is mandatory. Special attention has to be directed to osteolytic lesions in the periacetabular region as they can provoke pathological fractures and subsequent functional impairment. Different reconstruction techniques for the pelvis are available; the choice depends on the patient's prognosis, size of the bone defect, and response of the tumor to adjuvant treatment. If all the conservative treatments are exhausted and the patient is not eligible for surgery, one of the various percutaneous ablation procedures can be considered. We propose a pelvic analogue to the treatment algorithm in long bone metastasis and a scoring system in pelvic metastasis. This algorithm aims to simplify the teamwork and to avoid under- or overtreatment of pelvic bone metastases.

  12. The Surgical Treatment of Pelvic Bone Metastases

    Directory of Open Access Journals (Sweden)

    Daniel A. Müller

    2015-01-01

    Full Text Available Pelvic bone metastases are a growing concern in the field of orthopedic surgery. Patients with pelvic metastasis are individually different with different needs of treatment in order to attain the best possible quality of life despite the advanced stage of disease. A holistic collaboration among the oncologist, radiation therapist, and orthopedic surgeon is mandatory. Special attention has to be directed to osteolytic lesions in the periacetabular region as they can provoke pathological fractures and subsequent functional impairment. Different reconstruction techniques for the pelvis are available; the choice depends on the patient’s prognosis, size of the bone defect, and response of the tumor to adjuvant treatment. If all the conservative treatments are exhausted and the patient is not eligible for surgery, one of the various percutaneous ablation procedures can be considered. We propose a pelvic analogue to the treatment algorithm in long bone metastasis and a scoring system in pelvic metastasis. This algorithm aims to simplify the teamwork and to avoid under- or overtreatment of pelvic bone metastases.

  13. Complications and survival of megaprostheses after resection of bone metastases.

    Science.gov (United States)

    De Gori, M; D’Arienzo, A; Andreani, L; Beltrami, G; Campanacci, D A; De Biase, P; Frenos, F; Giannotti, S; Sacchetti, F; Totti, F; Parchi, P; Capanna, R

    Treatment of bone metastases is often palliative, aiming at pain control and stabilization or prevention of pathological fractures. However, a complete resection with healing purposes can be performed in selected cases. The aim of our work was to evaluate the survival of megaprostheses used for reconstruction after bone metastases. Between January 2001 and March 2015, we implanted 169 Megasystem-C® (Waldemar LINK® GmbH & Co. KG, Hamburg, Germany) after bone metastasis resection. Patients, 95 females and 74 males, were operated at an average age of 61 (12-87) years for proximal femoral resection in 135 (79.9%) cases, distal femur in 24 (14.2%), proximal tibia in 6 (3.6%), total femur in 3 (1.8%) and intercalary femur in 1 (0.6%). Mostly, breast cancer metastases (30.8%), kidney (17.8%) and lung (14.2%) were treated. At an average follow-up of 21 (1-150) months, we found a 99.4% overall limb salvage and a 96.1% overall survival rate at 1 year, 92.8% at 2 years, and 86.8% at 5 and 10 years. We found 9 (5.3%) mobilization cases of the proximal femoral implant, 3 needed surgical reduction; 2 (1.2%) cases of aseptic loosening of the prosthetic stem; 2 (1.2%) periprotetic infection cases, one requiring a 2-stage revision. Few literature studies have evaluated the survival of megaprosthetic implant in the treatment of bone metastases. Our data show how in this specific context the rate of complications is significantly lower than expected in general orthopedic orthopedic surgery. The use of modular prostheses is a valid reconstructive strategy after bone metastasis resection in selected patients. The rate of short-term complications is exceptionally low; further studies will have to confirm this in the longer term.

  14. Brain metastases from colorectal cancer

    DEFF Research Database (Denmark)

    Vagn-Hansen, Chris Aksel; Rafaelsen, Søren Rafael

    2001-01-01

    Brain metastases from colorectal cancer are rare. The prognosis for patients with even a single resectable brain metastasis is poor. A case of surgically treated cerebral metastasis from a rectal carcinoma is reported. The brain tumour was radically resected. However, cerebral, as well...... as extracerebral, disease recurred 12 months after diagnosis. Surgical removal of colorectal metastatic brain lesions in selected cases results in a longer survival time....

  15. Prevention of bone metastases in patients with high-risk nonmetastatic prostate cancer treated with zoledronic acid: efficacy and safety results of the Zometa European Study (ZEUS).

    Science.gov (United States)

    Wirth, Manfred; Tammela, Teuvo; Cicalese, Virgilio; Gomez Veiga, Francisco; Delaere, Karl; Miller, Kurt; Tubaro, Andrea; Schulze, Matthias; Debruyne, Frans; Huland, Hartwig; Patel, Anup; Lecouvet, Frederic; Caris, Christien; Witjes, Wim

    2015-03-01

    Patients with high-risk localised prostate cancer (PCa) are at risk of developing bone metastases (BMs). Zoledronic acid (ZA) significantly reduces the incidence of skeletal complications in castration-resistant metastatic PCa versus placebo. To investigate ZA for the prevention of BMs in high-risk localised PCa. Randomised open-label multinational study with patients having at least one of the following: prostate-specific antigen ≥20 ng/ml, node-positive disease, or Gleason score 8-10. Standard PCa therapy alone or combined with 4mg ZA intravenously every 3 mo for ≤4 yr. BMs were assessed using locally evaluated bone-imaging procedures (BIPs), with subsequent blinded central review. Patients with BMs, time to BMs, overall survival, and adverse events were compared between treatment groups. A total of 1393 of 1433 randomised patients were used for intention-to-treat (ITT) efficacy analyses, with 1040 patients with BIP-BM outcome status at 4±0.5 yr. The local urologist/radiologist diagnosed BIP-BMs in 88 of 515 patients (17.1%) in the ZA group and 89 of 525 patients (17.0%) in the control group (chi-square test: p=0.95), with a difference between proportions of 0.1% (95% confidence interval [CI], -4.4 to 4.7) in favour of the control group. In the ITT population (n=1393), the Kaplan-Meier estimated proportion of BMs after a median follow-up of 4.8 yr was 14.7% in the ZA group versus 13.2% in the control group (log-rank: p=0.65). Low hot spot numbers on bone scans were confirmed as metastases with additional imaging. Central reviews of BIPs were possible only on a subset of patients. ZA administered every 3 mo was demonstrated to be ineffective for the prevention of BMs in high-risk localised PCa patients at 4 yr. Zoledronic acid administered every 3 mo was demonstrated to be ineffective for the prevention of bone metastases in high-risk nonmetastatic PCa patients at 4 yr. The ZEUS trial is registered in the Dutch trial register www.trialregister.nl and the

  16. Skin metastases from lung cancer: a case report.

    Science.gov (United States)

    Pajaziti, Laura; Hapçiu, Syzana Rexhepi; Dobruna, Shkendije; Hoxha, Naim; Kurshumliu, Fisnik; Pajaziti, Artina

    2015-04-11

    Lung cancer is one of the most frequent malignancies, with high mortality rates. It can metastasize in almost all organs, but more often invades hilar nodes, liver, adrenal glands, bones and brain. There are various data on the incidence of lung cancer metastases in the skin. In 1-12% of patients with lung cancer are developed skin metastases. Metastases in the skin may be the first sign of lung cancer. Forty-five years old Albanian male, smoker, was admitted to our department with multiple nodules localized in the skin of the head, neck, back and chest. The nodules measuring 5-15 millimeters in greatest dimension were round and skin-colored, with telangiectasias, firm and tender. They appeared in an eruptive form about two weeks before being admitted at our hospital. In addition, the patient exhibited signs of weight loss, anorexia and fatigue. Excisional biopsy was performed to one of the lesions. Histopathology confirmed metastatic nature of the lesion namely, malignant tumor of neuroendocrine phenotype consistent with small-cell carcinoma. Chest X-ray and computed tomography revealed an expansive process in the 7(th) segment of the left lung, left hilar and mediastinal lymphadenopathy and a suspicious initial secondary deposit in the left adrenal gland. The patient was referred to the department of oncology for further treatment. After the third cycle of chemotherapy, the magnetic resonance imaging revealed brain metastases. The patient passed away four months after the diagnosis of lung cancer first presented with skin metastases. Metastases in skin may be the first sign of lung cancer. Although rare appearing, we should raise suspicion in cases of atypical lesions in the skin not only of the smokers, but also of the non-smokers. Skin metastases from small-cell lung carcinoma are a poor prognostic indicator. The appearance of multiple skin metastases with other internal metastases shorten the survival time.

  17. Increased expression of a set of genes enriched in oxygen binding function discloses a predisposition of breast cancer bone metastases to generate metastasis spread in multiple organs.

    Science.gov (United States)

    Capulli, Mattia; Angelucci, Adriano; Driouch, Keltouma; Garcia, Teresa; Clement-Lacroix, Philippe; Martella, Francesco; Ventura, Luca; Bologna, Mauro; Flamini, Stefano; Moreschini, Oreste; Lidereau, Rosette; Ricevuto, Enrico; Muraca, Maurizio; Teti, Anna; Rucci, Nadia

    2012-11-01

    Bone is the preferential site of distant metastasis in breast carcinoma (BrCa). Patients with metastasis restricted to bone (BO) usually show a longer overall survival compared to patients who rapidly develop multiple metastases also involving liver and lung. Hence, molecular predisposition to generate bone and visceral metastases (BV) represents a clear indication of poor clinical outcome. We performed microarray analysis with two different chip platforms, Affymetrix and Agilent, on bone metastasis samples from BO and BV patients. The unsupervised hierarchical clustering of the resulting transcriptomes correlated with the clinical progression, segregating the BO from the BV profiles. Matching the twofold significantly regulated genes from Affymetrix and Agilent chips resulted in a 15-gene signature with 13 upregulated and two downregulated genes in BV versus BO bone metastasis samples. In order to validate the resulting signature, we isolated different MDA-MB-231 clonal subpopulations that metastasize only in the bone (MDA-BO) or in bone and visceral tissues (MDA-BV). Six of the signature genes were also significantly upregulated in MDA-BV compared to MDA-BO clones. A group of upregulated genes, including Hemoglobin B (HBB), were involved in oxygen metabolism, and in vitro functional analysis of HBB revealed that its expression in the MDA subpopulations was associated with a reduced production of hydrogen peroxide. Expression of HBB was detected in primary BrCa tissue but not in normal breast epithelial cells. Metastatic lymph nodes were frequently more positive for HBB compared to the corresponding primary tumors, whereas BO metastases had a lower expression than BV metastases, suggesting a positive correlation between HBB and ability of bone metastasis to rapidly spread to other organs. We propose that HBB, along with other genes involved in oxygen metabolism, confers a more aggressive metastatic phenotype in BrCa cells disseminated to bone. Copyright © 2012

  18. Evaluation of bone metastases by 18F-choline PET/CT in a patient with castration-resistant prostate cancer treated with radium-223.

    Science.gov (United States)

    Scalzi, Piera; Baiocco, Cinzia; Genovese, Sabrina; Trevisan, Antonella; Sirotova, Zuzana; Poti, Carlo

    2017-02-03

    To date, bone metastases remain the main cause of morbidity and mortality in patients with metastatic castration-resistant prostate cancer (mCRPC). Therefore, the combination of accurate early detection of bony disease and effective treatment of these lesions is crucial in the management of mCRPC patients, but clinical trials specifically designed to test novel approaches are currently lacking. This report describes the case of a 74-year-old male with bone mCRPC and symptomatic and biochemical progression, who underwent radium-223 therapy, following previous treatment failure. 18F-choline positron emission tomography (PET)/computed tomography (CT) was used to assess changes in skeletal tumor activity before and after radium-223. Changes in prostate-specific antigen and alkaline phosphatase were also determined. 18F-choline PET/CT showed that treatment with radium-223 was able to effectively reduce bone metastatic disease, and this was accompanied by an excellent metabolic response. In clinical practice, metabolic assessment of lesions by 18F-choline PET/CT following radium-223 seems a valid approach to monitor treatment response. Until results from clinical trials become available, reporting of single cases relating to data on the use of this technique remains paramount.

  19. A new protocol of surgical treatment of long bone metastases.

    Science.gov (United States)

    Capanna, Rodolfo; De Biase, Pietro; Campanacci, Domenico A

    2003-06-30

    Background. The choice of proper treatment way is one of the most important things in surgically treated long bones metastases. The aim of this research was evaluation of the treatment way according to neoplasm's type and metastasis localisation and spreading. Material and methods. The evaluation underwent 158 patients who were divided in 4 groups. The first one consists of 13 patients with single metastasis of cancer with good prognosis. In the second group were 69 patients with bone fracture. The third group included 36 patients with such bone destruction that fracture was expected. The last fourth one had 40 patients with osteoblastic metastases or osteolitic in unloaded bones. Results and Discussion. In group I long lasting reconstructive implants are required and postoperative irradiation is recommended, in groups II and III the aggressiveness of treatment should be related to three parameters: survival expectancy, mechanical properties of the affected bone, predictive response to adjuvants. Based on the above parameters the quidelines of the protocol allow to identify the most appropriate reconstructive indication for every single case ranging from simple osteosynthesis (bad prognosis, low fracture risk, goodresponse to adjuvants) to prosthetic replacement (good prognosis, high fracture risk, bad response to adjuvants). Patients from group IV were admitted to oncology treatment ward after biopsy.

  20. Pathogenesis and pharmacological treatment of bone pain in skeletal metastases

    Energy Technology Data Exchange (ETDEWEB)

    Ripamonti, C. [National Cancer Institute, Rehabilitation, Pain Therapy and Palliative Care Division, Milan (Italy); Fulfaro, F. [Societa' per l' Assistenza al Malato Oncologico Terminale, Palermo (Italy)

    2001-03-01

    Sixty-five percent of patients with advanced cancer present bone metastases and most of them present a rather slow clinical course characterized by pain, mobility deficiencies and skeletal complications such as fractures and spinal cord compression. Metastatic involvement of the bone is one of the most frequent causes of pain in cancer patients and represents one of the firs signs of widespread neoplastic disease. The pain may originate directly from the plastic disease. The pain may originate directly from the bone, from nerve root compression or from muscle spasms in the area of the lesions. The mechanism of metastatic bone pain is mainly somatic (nociceptive) even though, in some cases, neuropathic and visceral stimulations may overlap. The conventional symptomatic treatment of metastatic bone pain requires the use of multidisciplinary therapies such as radiotherapy in association with systemic treatment (hormonotherapy, chemotherapy, radioisotopes) with the support of analgesic therapy. Recently, studies have indicated the use of bisphosphonates in the treatment of pain and in the prevention of skeletal complications in patients with metastatic bone disease. In some patients pharmacological treatment, radiotherapy, radioisotopes administered alone or in association are not able to manage pain adequately. The role of neuroinvasive techniques in treating metastatic bone pain is debated. The clinical conditions of the patient, his life expectancy and quality of life must guide the physician in the choice of the best possible therapy.

  1. {sup 177}Lu-EDTMP for palliation of pain from bone metastases in patients with prostate and breast cancer: a phase II study

    Energy Technology Data Exchange (ETDEWEB)

    Agarwal, Krishan Kant; Singla, Suhas; Arora, Geetanjali; Bal, Chandrasekhar [All India Institute of Medical Sciences, Department of Nuclear Medicine, Ansari Nagar, New Delhi (India)

    2015-01-15

    The purpose of this study was to evaluate the efficacy and safety of {sup 177}Lu-EDTMP for pain palliation in patients with bone metastases from castration-resistant prostate and breast cancer. The secondary objective was to compare low-dose and high-dose {sup 177}Lu-EDTMP in bone pain palliation. Included in the study were 44 patients with documented breast carcinoma (12 patients; age 47 ± 13 years) or castration-resistant prostate carcinoma (32 patients; age 66 ± 9 years) and skeletal metastases. Patients were randomized into two equal groups treated with {sup 177}Lu-EDTMP intravenously at a dose of 1,295 MBq (group A) or 2,590 MBq (group B). Pain palliation was evaluated using a visual analogue score (VAS), analgesic score (AS) and Karnofsky performance score (KPS) up to 16 weeks. Toxicity was assessed in terms of haematological and renal parameters. The overall response rate (in all 44 patients) was 86 %. Complete, partial and minimal responses were seen in 6 patients (13 %), 21 patients (48 %) and 11 patients (25 %), respectively. A favourable response was seen in 27 patients (84 %) with prostate cancer and in 11 patients (92 %) with breast cancer. There was a progressive decrease in the VAS from baseline up to 4 weeks (p < 0.05). Also, AS decreased significantly from 1.8 ± 0.7 to 1.2 ± 0.9 (p < 0.0001). There was an improvement in quality of life of the patients as reflected by an increase in mean KPS from 56 ± 5 to 75 ± 7 (p < 0.0001). The overall response rate in group A was 77 % compared to 95 % in group B (p = 0.188). There was a significant decrease in VAS and AS accompanied by an increase in KPS in both groups. Nonserious haematological toxicity (grade I/II) was observed in 15 patients (34 %) and serious toxicity (grade III/IV) occurred in 10 patients (23 %). There was no statistically significant difference in haematological toxicity between the groups. {sup 177}Lu-EDTMP was found to be a safe and effective radiopharmaceutical for bone pain

  2. Potential antiproliferative effect of isoxazolo- and thiazolo coumarin derivatives on breast cancer mediated bone and lung metastases

    Directory of Open Access Journals (Sweden)

    Ballazhi Lulzime

    2015-03-01

    Full Text Available The study highlights the current progress in the development of coumarin scaffolds for drug discovery as novel anticancer agents in metastatic breast cancer. Eight compounds, combining the coumarin core and five membered heterocycles (isoxazoles and thiazoles in hydrazinyldiene- -chroman-2,4-diones, were characterized in terms of a potential antiproliferative effect on bone (SCP1833 and lung (SCP4175 metastatic breast cancer cell lines using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. Cell viability was evaluated after 48 and 72 h of treatment and the 50 % inhibitory concentrations were determined. The results demonstrated dose- and time-dependent activity, with the most potent molecules having a thiazole moiety, without or with additional methyl group(s attached to the carbon(s at position(s 5 and/or 4 in the thiazole ring. These molecules possessed significantly higher potency against both test cell lines compared to 4-hydroxycoumarin

  3. Imaging response during therapy with radium-223 for castration-resistant prostate cancer with bone metastases-analysis of an international multicenter database

    DEFF Research Database (Denmark)

    Keizman, D; Fosboel, M O; Reichegger, H

    2017-01-01

    BACKGROUND: The imaging response to radium-223 therapy is at present poorly described. We aimed to describe the imaging response to radium-223 treatment. METHODS: We retrospectively evaluated the computed tomography (CT) and bone scintigraphy response of metastatic castration-resistant prostate...... of 54% (n=70) patients completed the planned six injections of radium-223. In patients with available data, a transient increase in bone metastases-related pain was observed in 27% (n=33/124) and an improvement of bone metastases-related pain on treatment with radium-223 was noted in 49% of patients (n......=61/124). At 3 and 6 months of treatment with radium-223, bone imaging showed stable disease in 74% (n=84/113) and 94% of patients (n=93/99) with available data, respectively. An increase in the number of bone lesions was documented at 3 months compared with baseline in 26% (n=29/113) and at 6 months...

  4. HPMA Copolymer-Conjugated Pirarubicin in Multimodal Treatment of a Patient with Stage IV Prostate Cancer and Extensive Lung and Bone Metastases.

    Science.gov (United States)

    Dozono, Haruhiko; Yanazume, Shintaro; Nakamura, Hideaki; Etrych, Tomáš; Chytil, Petr; Ulbrich, Karel; Fang, Jun; Arimura, Takeshi; Douchi, Tsutomu; Kobayashi, Hiroaki; Ikoma, Michiaki; Maeda, Hiroshi

    2016-02-01

    Nanomedicine allows achievement of tumor-selective drug delivery because of the enhanced permeability and retention (EPR) effect of solid tumors. We report here the first clinical application of a new agent-HPMA copolymer-conjugated pirarubicin (P-THP)-with a molecular size of about 8 nm, or 38.5 kDa. A patient had advanced prostate cancer with multiple metastases in the lung, pelvis, femur, and perhaps the sacrum. In April 2013, this 60-year-old patient started treatment with leuprorelin and estradiol, which continued until July 2014, but the patient became refractory to this treatment. So the patient underwent proton beam radiotherapy targeted to the primary prostate cancer, and P-THP was administered for numerous metastatic tumor nodules concomitantly with radiotherapy. This combination therapy had remarkable results, with complete remission of multiple metastases in the lung and bone. The prostate-specific antigen (PSA) value was decreased from about 1000 ng/mL on April 30, 2013, to about 100 ng/mL on June 24, 2013, with hormone therapy, but rose again to 964.2 ng/mL and then to 1472 ng/mL in July 2013, during leuprorelin administration. P-THP treatment administered concomitantly with proton beam irradiation was started in August 2013. The PSA value was decreased to 102 ng/mL on August 26, 2013, and then to 0.971 ng/mL on October 8, 2013, and 0.277 ng/mL on January 15, 2015. The P-THP doses ranged from 30 to 75 mg of free THP equivalent/patient every 2-3 weeks without signs of serious toxicity, such as cardiovascular side effects or a reduction in quality of life. No evidence of relapse was found more than 20 months after P-THP administration. This case demonstrates the value of hydrazone-bonded polymeric drugs in multimodal therapy.

  5. Translation into Portuguese, cross-cultural adaptation and validation of "The European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire-Bone Metastases-22".

    Science.gov (United States)

    Miki-Rosário, Natália; Garcia Filho, Reynaldo Jesus; Garcia, Jairo Greco; Dini, Gal Moreira; Bottomley, Andrew; Chow, Edward; Sabino Neto, Miguel

    2016-07-01

    The aim of the present study was to conduct a cross-cultural adaptation (with translation into Brazilian Portuguese) and validation of the European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire-Bone Metastases-22 (EORTC QLQ-BM22). Ninety-five bone metastasis patients (31 men and 64 women, mean age 58.36±8.90 years) took part in the investigation. The translation guide of the EORTC was used to translate from English into Brazilian Portuguese and adapt the instrument culturally. The reliability and the face, content and construct validities were tested. Internal consistency was estimated using Cronbach's alpha for the total score, pain and functional subscales of the EORTC QLQ-BM22 (0.93, 0.86, 0.90). Reliability was analyzed by Pearson's correlation and intraclass correlation coefficients (ICCs). The correlations were higher than the recommended value of 0.75, which indicated good test-retest reliability. Construct validity was demonstrated by correlation with the questionnaire medical outcome study questionnaire 36-Item Short Form Survey (SF-36). It showed significant correlation between the fields of QLQ-BM22 and the SF-36 (P≤0.001). The EORTC QLQ-BM22 was translated into Brazilian Portuguese, was culturally adapted and was proven to be reliable, with face, content and construct validity.

  6. Suppression of NADPH Oxidase Activity May Slow the Expansion of Osteolytic Bone Metastases

    Directory of Open Access Journals (Sweden)

    Mark F. McCarty

    2016-08-01

    Full Text Available Lysophosphatidic acid (LPA, generated in the microenvironment of cancer cells, can drive the proliferation, invasion, and migration of cancer cells by activating G protein-coupled LPA receptors. Moreover, in cancer cells that have metastasized to bone, LPA signaling can promote osteolysis by inducing cancer cell production of cytokines, such as IL-6 and IL-8, which can stimulate osteoblasts to secrete RANKL, a key promoter of osteoclastogenesis. Indeed, in cancers prone to metastasize to bone, LPA appears to be a major driver of the expansion of osteolytic bone metastases. Activation of NADPH oxidase has been shown to play a mediating role in the signaling pathways by which LPA, as well as RANKL, promote osteolysis. In addition, there is reason to suspect that Nox4 activation is a mediator of the feed-forward mechanism whereby release of TGF-beta from bone matrix by osteolysis promotes expression of PTHrP in cancer cells, and thereby induces further osteolysis. Hence, measures which can down-regulate NADPH oxidase activity may have potential for slowing the expansion of osteolytic bone metastases in cancer patients. Phycocyanin and high-dose statins may have utility in this regard, and could be contemplated as complements to bisphosphonates or denosumab for the prevention and control of osteolytic lesions. Ingestion of omega-3-rich flaxseed or fish oil may also have potential for controlling osteolysis in cancer patients.

  7. Complications of bone metastases from malignant melanoma

    Directory of Open Access Journals (Sweden)

    Jamal Zekri

    2017-09-01

    Conclusion: MBD affects a clinically important proportion (17.2% of patients with metastatic MM. It carries a substantial morbidity and mortality exceeding that caused by BMs from breast and prostate cancer. These patients should receive the currently licensed bone modifying agents and should be included in clinical trials addressing MBD.

  8. Multimodality imaging of TGFβ signaling in breast cancer metastases

    Science.gov (United States)

    Serganova, Inna; Moroz, Ekaterina; Vider, Jelena; Gogiberidze, George; Moroz, Maxim; Pillarsetty, Nagavarakishore; Doubrovin, Michael; Minn, Andy; Thaler, Howard T.; Massague, Joan; Gelovani, Juri; Blasberg, Ronald

    2009-01-01

    The skeleton is a preferred site for breast cancer metastasis. We have developed a multimodality imaging approach to monitor the transforming growth factor β (TGFβ) signaling pathway in bone metastases, sequentially over time in the same animal. As model systems, two MDA-MB-231 breast cancer cells lines with different metastatic tropisms, SCP2 and SCP3, were transduced with constitutive and TGFβ-inducible reporter genes and were tested in vitro and in living animals. The sites and expansion of metastases were visualized by bioluminescence imaging using a constitutive firefly luciferase reporter, while TGFβ signaling in metastases was monitored by microPET imaging of HSV1-TK/GFP expression with [18F]FEAU and by a more sensitive and cost-effective bioluminescence reporter, based on nonsecreted Gaussia luciferase. Concurrent and sequential imaging of metastases in the same animals provided insight into the location and progression of metastases, and the timing and course of TGFβ signaling. The anticipated and newly observed differences in the imaging of tumors from two related cell lines have demonstrated that TGFβ signal transduction pathway activity can be noninvasively imaged with high sensitivity and reproducibility, thereby providing the opportunity for an assessment of novel treatments that target TGFβ signaling.—Serganova, I., Moroz, E., Vider, J., Gogiberidze, G., Moroz, M., Pillarsetty, N., Doubrovin, M., Minn, A., Thaler, H. T., Massague, J., Gelovani, J., Blasberg, R. Multimodality imaging of TGFβ signaling in breast cancer metastases. PMID:19325038

  9. Percutaneous radiofrequency ablation in painful bone metastases

    Directory of Open Access Journals (Sweden)

    German Garabano

    2015-09-01

    Full Text Available Backgraund There are different treatment for painful bone metastases (mtts, with different results. CT-guided Percutaneous Radiofrequency Ablation (CT-PRA is one of them. The pupose of this retrospective study was to assess the initial results using this methods, focusing on pain relief, showing details of the surgical technique. Methods 18 patients with an average age of 59.2 years and 15 months follow-up were treated. Nine mtts were located in the femur, 4 dorsal / lumbar spine, 3 in scapula and 2 in Iliac. The Mtts origin were Breast Ca 7 cases, lung in 4, Kidney in 4 and 3 in Thyroid. The rachis mtts were found at more than 10mm of the medullary cavity and mtts of long bones showed low risk of fracture. Lesions >3cm were treated whit CT-PRA  using Valleylab Rita needle and these <3cm with CoolTip needle. Pain was assessed by Visual Analog Scale (VAS preoperatively, at 2, 7 and 30 days, and then at 3 and 6 months. Results Preoperative pain score was 8.33 on average. At 7 days of ablatión de VAS score was 5 on average and at 30 days was 2 points. After at 3 and 6 months de VAS average was 1. This method had excellent patients tolerance and no complications. There were two recurrences which underwent endoprosthesis unconventional proximal femur and knee respectively, evolving favorably. Conclusion CT-guided APRF impresses a promising, simple and effective tool in the treatment of painfull bone mtts, achieving excellent pain control with good tolerance by the patient.

  10. Epidermal growth factor receptor mutations should be considered as a prognostic factor for survival of patients with pathological fractures or painful bone metastases from non-small cell lung cancer.

    Science.gov (United States)

    Willeumier, J J; van der Hoeven, N M A; Bollen, L; Willems, L N A; Fiocco, M; van der Linden, Y M; Dijkstra, P D S

    2017-04-01

    This study aims to assess first, whether mutations in the epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma (kRAS) genes are associated with overall survival (OS) in patients who present with symptomatic bone metastases from non-small cell lung cancer (NSCLC) and secondly, whether mutation status should be incorporated into prognostic models that are used when deciding on the appropriate palliative treatment for symptomatic bone metastases. We studied 139 patients with NSCLC treated between 2007 and 2014 for symptomatic bone metastases and whose mutation status was known. The association between mutation status and overall survival was analysed and the results applied to a recently published prognostic model to determine whether including the mutation status would improve its discriminatory power. The median OS was 3.9 months (95% confidence interval (CI) 2.1 to 5.7). Patients with EGFR (15%) or kRAS mutations (34%) had a median OS of 17.3 months (95% CI 12.7 to 22.0) and 1.8 months (95% CI 1.0 to 2.7), respectively. Compared with EGFR-positive patients, EGFR-negative patients had a 2.5 times higher risk of death (95% CI 1.5 to 4.2). Incorporating EGFR mutation status in the prognostic model improved its discriminatory power. Survival prediction models for patients with symptomatic bone metastases are used to determine the most appropriate (surgical) treatment for painful or fractured lesions. This study shows that NSCLC should not be regarded as a single entity in such models. Cite this article: Bone Joint J 2017;99-B:516-21. ©2017 The British Editorial Society of Bone & Joint Surgery.

  11. Metastasic bone pain management with radioactive isotopes

    Directory of Open Access Journals (Sweden)

    Juan Coya Viña

    2005-10-01

    Full Text Available Pain is the commonest clinical manifestation of bone metastases. Its treatment is palliative in nature, and consists of chemotherapy, radiotherapy, hormonotherapy, diphosphonates, and drug therapy (i. e., opiates. Radioactive isotopes represent an appealing alternative to conventional treatment modalities. Among the different types of isotopes, wide clinical experience with 153Sm has been obtained in this laboratory. In the present study, 94 patients (mean age = 65 years, who had been diagnosed of having breast, prostate and other malignant tumors, were evaluated. These patients were treated with 37 MBq/Kg 153Sm-EDTMP. All of them complained of bone pain and had scintigraphic evidence of metastatic bone dissemination. Treatment efficacy was evaluated both objectively and subjectively. Eighty-five per cent (85% of the patients reported pain relief, and analgesia was reduced by 55%. Twenty-two per cent (22% had a complete response. Bone marrow toxicity was not a concern, with mild transient hematologic derangements in 30% of the patients. It was concluded that 153Sm-EDTMP results in relief or cessation of metastatic bone pain in a majority of patients.A dor é a manifestação clínica mais comum da metástase óssea. Seu tratamento é, por natureza, paliativo e consiste de quimioterapia, radioterapia, hormonoterapia, difosfonatos, e terapia medicamentosa (i.e.opiáceos. Isótopos radioativos representam uma alternativa atraente para as modalidades covencionais de tratamento. Entre os diferentes tipos de isótopos, temos grande experiência clínica com 153Sm. Neste estudo, nós avaliamos 94 pacientes na faixa de 65 anos com diagnóstico de cânceres de próstata, de mamas e outros tumores malignos. Esses pacientes foram tratados com 37 MBq/Kg de 153Sm-EDTMP. Todos eles reclamavam de dor nos ossos e apresentavam evidências de disseminação de metástase óssea. O tratamento foi analisado objetivamente e subjetivamente. Oitenta e cinco (85% dos

  12. Bone metastases of unknown origin: epidemiology and principles of management

    National Research Council Canada - National Science Library

    Piccioli, Andrea; Maccauro, Giulio; Spinelli, Maria Silvia; Biagini, Roberto; Rossi, Barbara

    2015-01-01

    ... % of patients present with bone metastases of unknown origin, where the site of the primary neoplasm cannot be identified at the time of diagnosis despite a thorough history, physical examination...

  13. Bone health in cancer patients

    DEFF Research Database (Denmark)

    Coleman, R; Body, J J; Aapro, M

    2014-01-01

    There are three distinct areas of cancer management that make bone health in cancer patients of increasing clinical importance. First, bone metastases are common in many solid tumours, notably those arising from the breast, prostate and lung, as well as multiple myeloma, and may cause major...... cancer for many patients resulting in a major reduction in skeletal complications, reduced bone pain and improved quality of life. Secondly, many of the treatments we use to treat cancer patients have effects on reproductive hormones, which are critical for the maintenance of normal bone remodelling....... This endocrine disturbance results in accelerated bone loss and an increased risk of osteoporosis and fractures that can have a significant negative impact on the lives of the rapidly expanding number of long-term cancer survivors. Finally, the bone marrow micro-environment is also intimately involved...

  14. Osteopoikilosis: A Sign Mimicking Skeletal Metastases in a Cancer Patient

    Directory of Open Access Journals (Sweden)

    Hamid Nasrolahi

    2011-01-01

    Full Text Available Osteopoikilosis is a rare benign osteosclerotic bone disorder that may be misdiagnosed as skeletal metastases. Here we describe a case of coincidental breast cancer and osteopoikilosis mimicking skeletal metastases. A 41-year-old woman underwent right modified radical mastectomy in April 2007. Twenty-eight months after initial treatment,the patient complained of bilateral knee and foot pain. Plain X-rays of the feet and knees showed multiple well-defined osteosclerotic lesions. According to the radiographic appearance, the most likely differential diagnoses included skeletal metastases from breast cancer and osteopoikilosis. A whole-body bone scintigraphy showed no increase in uptake by the sclerotic lesions, and serum lactic dehydrogenase, carcinoembryonic antigen, alkaline phosphatase and cancer antigen 15-3 were not elevated. We therefore diagnosed the patient’s skeletal lesions as osteopoikilosis. This case and ourliterature review suggest that the radiographic appearance of osteopoikilosis may mimic or mask skeletal metastases, potentially leading to misdiagnosis in patients with cancer.

  15. Prevalence of Vitamin D Deficiency in Patients with Bone Metastases and Multiple Myeloma.

    Science.gov (United States)

    Maier, Gerrit Steffen; Horas, Konstantin; Kurth, Andreas Alois; Lazovic, Djordje; Seeger, Jörn Bengt; Maus, Uwe

    2015-11-01

    Breast and prostate cancer are amongst the most prevalent malignancies globally and up to 40% of patients will develop metastatic disease, particularly to the skeleton. Multiple myeloma is the most common cancer to affect bone with up to 90% of patients developing bone lesions. Although several studies demonstrated that endocrine changes such as vitamin D deficiency promote secondary cancer growth in bone, relatively few have reported its prevalence. For this reason, the purpose of the present study was to evaluate the prevalence of hypovitaminosis D in patients with bone metastases and multiple myeloma. Serum 25-OH-D levels of patients with metastatic bone disease were measured on admission. Statistical analyses was performed to evaluate for possible confounders of hypo-vitaminosis D. We found a widespread and alarming rate of vitamin D deficiency in patients with metastatic bone disease and multiple myeloma. Of note, patients with bone metastases due to breast cancer, prostate cancer and multiple myeloma rarely reached sufficient serum 25-OH-D levels. It is of utmost clinical importance to assess vitamin D levels in cancer patients, especially in those with, or at high risk of developing metastatic bone disease. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  16. Papillary thyroid carcinoma presenting as an asymptomatic pelvic bone metastases

    Directory of Open Access Journals (Sweden)

    Siddiq S

    2010-05-01

    Full Text Available Thyroid carcinoma is rare comprising 1% of all malignancies and commonly presents as a neck lump. Papillary thyroid carcinoma unlike follicular thyroid carcinoma tends not to metastasise to distant sites.We present a case of papillary thyroid carcinoma presenting as a solitary asymptomatic pelvic bone metastases and highlight current management of bone metastases. A 59-year old female was found on abdominal computerised tomography to have an incidental finding of a 4.5 cm soft tissue mass in the right iliac bone. Biopsy of the lesion confirmed metastatic thyroid carcinoma. There was no history of a neck lump, head and neck examination was normal. Further imaging confirmed focal activity in the right lobe of the thyroid. A total thyroidectomy and level VI neck dissection was performed and histology confirmed follicular variant of papillary carcinoma.Early detection of bone metastases have been shown to improve prognosis and thyroid carcinoma should be considered as a potential primary malignancy.

  17. Quality of Life in Relation to Pain Response to Radiation Therapy for Painful Bone Metastases

    NARCIS (Netherlands)

    Westhoff, Paulien G.; De Graeff, Alexander|info:eu-repo/dai/nl/187695997; Monninkhof, Evelyn M.|info:eu-repo/dai/nl/260610178; Pomp, Jacqueline; Van Vulpen, Marco|info:eu-repo/dai/nl/250581035; Leer, Jan Willem H; Marijnen, Corrie A M; Van Der Linden, Yvette M.

    2015-01-01

    Purpose: To study quality of life (QoL) in responders and nonresponders after radiation therapy for painful bone metastases; and to identify factors predictive for a pain response. Patients and Methods: The prospectively collected data of 956 patients with breast, prostate, and lung cancer within

  18. Quality of Life in Relation to Pain Response to Radiation Therapy for Painful Bone Metastases

    NARCIS (Netherlands)

    Westhoff, P.G.; Graeff, A. de; Monninkhof, E.M.; Pomp, J.; Vulpen, M. van; Leer, J.W.; Marijnen, C.A.; Linden, Y.M. van der

    2015-01-01

    PURPOSE: To study quality of life (QoL) in responders and nonresponders after radiation therapy for painful bone metastases; and to identify factors predictive for a pain response. PATIENTS AND METHODS: The prospectively collected data of 956 patients with breast, prostate, and lung cancer within

  19. Biochemical parameters of bone metabolism in bone metastases of solid tumors (Review)

    NARCIS (Netherlands)

    Meijer, Wilhelmus; van der Veer, E; Willemse, P H

    1998-01-01

    The role of biochemical markers of bone metabolism in the diagnosis and monitoring of bone metastases in solid tumors is reviewed. Emphasis is on the recently developed markers, which may provide a more accurate quantitation of bone metabolism. In metastatic bone disease, bone formation and

  20. Surgical treatment of metastasic tumors to long bones in the material of the Unit.

    Science.gov (United States)

    Karwicki, Lech; Kmieciak, Marek; Kopka, Maciej

    2003-06-30

    Background. Neoplasms of limbs are appear as primary of changes or as bone metastases. Material and methods. In 1989-2002 due to neoplasms limbs 795 patients were hospitalised, of which 278 suffered from malignant metastases to bones. In this group, 242 patients with lesions localised within the femoral (169), humeral (55) and tibial (18) bones were identified. In 75% of patients pathological fractures were diagnosed, in the remaining ones the metastasis was manifested in the form of osteolytic lesion. In most cases early surgical treatment was performed to eliminate pain complaints, improve patient's physical mobility through restoration of limb functions and also to enable nursing care to be performed in palliative management. The choice of treatment method depended on: location of metastasis, degree of bone tissue destruction, type of primary tumour, progression of malignant process and technical resources. Within the long bones intramedullary nails (189) of different generations were implanted. In the proximal part of femoral bone various types of endoprostheses (65) were used, enabling oncological radicalism and early rehabilitation of the patients. Results. Resection of bones with neoplasm-induced lesions, filling the lesion with bony cement and stabilisation with blocking nails permitted early rehabilitation of patients. In our material the most common malignancies inducing metastases were: breast, kidney, lung cancers and myeloma. Patients with these neoplasms constituted nearly 74% of all hospitalised subjects. Conclusions. Necessity of systemic management and importance of early surgical treatment of metastases in specialized centres were underlined.

  1. Imaging of metastases from breast cancer to uncommon sites: a pictorial review.

    Science.gov (United States)

    Toguchi, Masafumi; Matsuki, Mitsuru; Numoto, Isao; Tsurusaki, Masakatsu; Imaoka, Izumi; Ishii, Kazunari; Yamashita, Rikiya; Inada, Yuki; Monzawa, Shuichi; Kobayashi, Hisato; Murakami, Takamichi

    2016-06-01

    There are three types of breast cancer recurrence which can occur after initial treatment: local, regional, and distant. Distant metastases are more frequent than local and regional recurrences. It usually occurs several years after the primary breast cancer, although it is sometimes diagnosed at the same time as the primary breast cancer. Although the common distant metastases are bone, lung and liver, breast cancer has the potential to metastasize to almost any region of the body. Early detection and treatment of distant metastases improves the prognosis, therefore radiologists and clinicians should recognize the possibility of metastasis from breast cancer and grasp the imaging characteristics. In this report, we demonstrate the imaging characteristics of metastases from breast cancer to uncommon sites.

  2. The flavonoid p-hydroxycinnamic acid mediates anticancer effects on MDA-MB-231 human breast cancer cells in vitro: Implications for suppression of bone metastases.

    Science.gov (United States)

    Yamaguchi, Masayoshi; Murata, Tomiyasu; Shoji, Mamoru; Weitzmann, M Neale

    2015-10-01

    Tumor invasion into bone tissues is associated with osteoclast and osteoblast recruitment, resulting in the liberation of growth factors from the bone matrix, which can feed back to enhance tumor growth resulting in the vicious cycle of bone metastasis. Activated nuclear factor-κB (NF-κB) in breast cancer cells has been shown to play a crucial role in the osteolytic bone metastasis of breast cancer in stimulating osteoclastogenesis. The flavonoid p-hydroxycinnamic acid (HCA) mediates bone anabolic and anti-catabolic effects by stimulating osteoblastic bone formation and suppressing osteoclastic bone resorption. However, the capacity of HCA to ameliorate the negative effects of breast cancer on bone cells has not been investigated. The present study was undertaken to determine the anticancer effects of HCA on MDA-MB-231 human breast cancer bone metastatic cells in vitro models. Proliferation of MDA-MB‑231 cells was suppressed by culture with HCA (10-1000 nM) due to G1 and G2/M phase cell cycle arrest. The suppressive effects of HCA were mediated through signaling pathways that are related to NF-κB, extracellular signal-regulated kinase (ERK), protein kinase C, calcium signaling, phosphatidylinositol 3-kinase (PI3K) and nuclear transcription activity. HCA was also found to induce death of confluent cancer cells. Furthermore, co-culture with MDA-MB-231 cells suppressed mineralization and stimulated osteoclastogenesis in bone marrow cells. These alterations were prevented by HCA (10-250 nM). The present study demonstrates that HCA possesses anticancer properties in MDA-MB-231 human breast cancer cells and alleviates the negative effects on osteoblastogenesis and osteoclastogenesis in vitro. HCA may have important applications in the treatment of breast cancer bone metastasis.

  3. Effect of radium-223 dichloride on symptomatic skeletal events in patients with castration-resistant prostate cancer and bone metastases: results from a phase 3, double-blind, randomised trial.

    Science.gov (United States)

    Sartor, Oliver; Coleman, Robert; Nilsson, Sten; Heinrich, Daniel; Helle, Svein I; O'Sullivan, Joe M; Fosså, Sophie D; Chodacki, Aleš; Wiechno, Paweł; Logue, John; Widmark, Anders; Johannessen, Dag Clement; Hoskin, Peter; James, Nicholas D; Solberg, Arne; Syndikus, Isabel; Vogelzang, Nicholas J; O'Bryan-Tear, C Gillies; Shan, Minghua; Bruland, Øyvind S; Parker, Christopher

    2014-06-01

    Bone metastases frequently cause skeletal events in patients with metastatic castration-resistant prostate cancer. Radium-223 dichloride (radium-223) selectively targets bone metastases with high-energy, short-range α-particles. We assessed the effect of radium-223 compared with placebo in patients with castration-resistant prostate cancer and bone metastases. In this phase 3, double-blind, randomised ALSYMPCA trial, we enrolled patients who had symptomatic castration-resistant prostate cancer with two or more bone metastases and no known visceral metastases, who were receiving best standard of care, and had previously either received or were unsuitable for docetaxel. Patients were stratified by previous docetaxel use, baseline total alkaline phosphatase level, and current bisphosphonate use, then randomly assigned (2:1) to receive either six intravenous injections of radium-223 (50 kBq/kg) or matching placebo; one injection was given every 4 weeks. Randomisation was done with an interactive voice response system, taking into account trial stratification factors. Participants and investigators were masked to treatment assignment. The primary endpoint was overall survival, which has been reported previously. Here we report on time to first symptomatic skeletal event, defined as the use of external beam radiation to relieve bone pain, or occurrence of a new symptomatic pathological fracture (vertebral or non-verterbal), or occurence of spinal cord compression, or tumour-related orthopeadic surgical intervention. All events were required to be clinically apparent and were not assessed by periodic radiological review. Statistical analyses of symptomatic skeletal events were based on the intention-to-treat population. The study has been completed and is registered with ClinicalTrials.gov, number NCT00699751. Between June 12, 2008, and Feb 1, 2011, 921 patients were enrolled, of whom 614 (67%) were randomly assigned to receive radium-223 and 307 (33%) placebo

  4. Targeting G-Protein Signaling for the Therapeutics of Prostate Tumor Bone Metastases and the Associated Chronic Bone Pain

    Science.gov (United States)

    2015-09-01

    Cancer Bone Metastasis, heterotrimeric G protein  subunits, G protein -coupled receptors, signal transduction 16. SECURITY CLASSIFICATION OF: 17...comparable to that of Gαt-expressing cells (Fig.2A), indicating the involvement of G subunits released from Gi/o proteins . Interestingly, the growth...1 AWARD NUMBER: W81XWH-12-1-0213 TITLE: Targeting G- Protein Signaling for the Therapeutics of Prostate Tumor Bone Metastases and the

  5. Treatment of bone pain secondary to metastases using samarium-153-EDTMP

    Directory of Open Access Journals (Sweden)

    Elba Cristina Sá de Camargo Etchebehere

    Full Text Available CONTEXT: More than 50% of patients with prostate, breast or lung cancer will develop painful bone metastases. The purpose of treating bone metastases is to relieve pain, reduce the use of steroids and to maintain motion. OBJECTIVE: To evaluate the use of samarium-153-EDTMP (153Sm-EDTMP for the treatment of bone pain secondary to metastases that is refractory to clinical management. TYPE OF STUDY: Retrospective. SETTING: Division of Nuclear Medicine, Universidade Estadual de Campinas (Unicamp. METHODS: Fifty-eight patients were studied (34 males with mean age 62 years; 31 patients had prostate cancer, 20 had breast cancer, three had lung cancer, one had lung hemangioendothelioma, one had parathyroid adenocarcinoma, one had osteosarcoma and one had an unknown primary tumor. All patients had multiple bone metastases demonstrated by bone scintigraphy using 99mTc-MDP,and were treated with 153Sm-EDTMP. Response to treatment was graded as good (pain reduction of 50-100%, intermediate (25-49% and poor (0-24%. RESULTS: All patients showed good uptake of 153Sm-EDTMP by bone metastases. Among the patients with prostate cancer, intermediate or good response to therapy occurred in 80.6% (25 patients and poor response in 19.4% (6. Among the patients with breast cancer, 85% (17 showed intermediate or good response to therapy while 15% (3 showed poor response. All three patients with lung cancer showed poor response to treatment. The lung hemangioendothelioma and unknown primary lesion patients showed intermediate response to treatment; the osteosarcoma and parathyroid adenocarcinoma patients showed good response to treatment. No significant myelotoxicity occurred. DISCUSSION: Pain control is important for improving the quality of life of patients with advanced cancers. The mechanism by which pain is relieved with the use of radionuclides is still not yet completely understood, however, the treatment is simple and provides a low risk of mielotoxicity

  6. Bone marrow fat: linking adipocyte-induced inflammation with skeletal metastases.

    Science.gov (United States)

    Hardaway, Aimalie L; Herroon, Mackenzie K; Rajagurubandara, Erandi; Podgorski, Izabela

    2014-09-01

    Adipocytes are important but underappreciated components of bone marrow microenvironment, and their numbers greatly increase with age, obesity, and associated metabolic pathologies. Age and obesity are also significant risk factors for development of metastatic prostate cancer. Adipocytes are metabolically active cells that secrete adipokines, growth factors, and inflammatory mediators; influence behavior and function of neighboring cells; and have a potential to disturb local milleu and dysregulate normal bone homeostasis. Increased marrow adiposity has been linked to bone marrow inflammation and osteoporosis of the bone, but its effects on growth and progression of prostate tumors that have metastasized to the skeleton are currently not known. This review focuses on fat-bone relationship in a context of normal bone homeostasis and metastatic tumor growth in bone. We discuss effects of marrow fat cells on bone metabolism, hematopoiesis, and inflammation. Special attention is given to CCL2- and COX-2-driven pathways and their potential as therapeutic targets for bone metastatic disease.

  7. Osthole inhibits bone metastasis of breast cancer

    OpenAIRE

    Wu, Chunyu; Sun, Zhenping; Guo, Baofeng; Ye, Yiyi; Han, Xianghui; Qin, Yuenong; Liu, Sheng

    2017-01-01

    Bone is one of the most common sites for breast cancer metastasis, which greatly contributes to patient morbidity and mortality. Osthole, a major extract from Cnidium monnieri (L.), exhibits many biological and pharmacological activities, however, its potential as a therapeutic agent in the treatment of breast cancer bone metastases remain poorly understood. In this study, we set out to investigate whether osthole could inhibit breast cancer metastasis to bone in mice and clarified the potent...

  8. Efficacy of Radiotherapy for Painful Bone Metastases During the Last 12 Weeks of Life

    NARCIS (Netherlands)

    Meeuse, Jan J.; van der Linden, Yvette M.; van Tienhoven, Geertjan; Gans, Rijk O. B.; Leer, Jan Willem H.; Reyners, An K. L.

    2010-01-01

    BACKGROUND: Radiotherapy is an effective treatment for painful bone metastases. Whether this applies also in patients with limited survival remains to be investigated. This study analyzed the effect of radiotherapy for painful bone metastases in patients with a survival

  9. Palliative radiotherapy for bone metastases: an ASTRO evidence-based guideline.

    Science.gov (United States)

    Lutz, Stephen; Berk, Lawrence; Chang, Eric; Chow, Edward; Hahn, Carol; Hoskin, Peter; Howell, David; Konski, Andre; Kachnic, Lisa; Lo, Simon; Sahgal, Arjun; Silverman, Larry; von Gunten, Charles; Mendel, Ehud; Vassil, Andrew; Bruner, Deborah Watkins; Hartsell, William

    2011-03-15

    To present guidance for patients and physicians regarding the use of radiotherapy in the treatment of bone metastases according to current published evidence and complemented by expert opinion. A systematic search of the National Library of Medicine's PubMed database between 1998 and 2009 yielded 4,287 candidate original research articles potentially applicable to radiotherapy for bone metastases. A Task Force composed of all authors synthesized the published evidence and reached a consensus regarding the recommendations contained herein. The Task Force concluded that external beam radiotherapy continues to be the mainstay for the treatment of pain and/or prevention of the morbidity caused by bone metastases. Various fractionation schedules can provide significant palliation of symptoms and/or prevent the morbidity of bone metastases. The evidence for the safety and efficacy of repeat treatment to previously irradiated areas of peripheral bone metastases for pain was derived from both prospective studies and retrospective data, and it can be safe and effective. The use of stereotactic body radiotherapy holds theoretical promise in the treatment of new or recurrent spine lesions, although the Task Force recommended that its use be limited to highly selected patients and preferably within a prospective trial. Surgical decompression and postoperative radiotherapy is recommended for spinal cord compression or spinal instability in highly selected patients with sufficient performance status and life expectancy. The use of bisphosphonates, radionuclides, vertebroplasty, and kyphoplasty for the treatment or prevention of cancer-related symptoms does not obviate the need for external beam radiotherapy in appropriate patients. Radiotherapy is a successful and time efficient method by which to palliate pain and/or prevent the morbidity of bone metastases. This Guideline reviews the available data to define its proper use and provide consensus views concerning contemporary

  10. Tumor Response After Stereotactic Body Radiation Therapy to Nonspine Bone Metastases: An Evaluation of Response Criteria

    Energy Technology Data Exchange (ETDEWEB)

    McDonald, Rachel [Department of Radiation Oncology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada); Probyn, Linda [Department of Medical Imaging, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada); Poon, Ian; Erler, Darby; Brotherston, Drew; Soliman, Hany; Cheung, Patrick; Chung, Hans; Chu, William; Loblaw, Andrew; Thavarajah, Nemica [Department of Radiation Oncology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada); Lang, Catherine [Department of Medical Imaging, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada); Chin, Lee [Department of Physics, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada); Chow, Edward, E-mail: Edward.Chow@sunnybrook.ca [Department of Radiation Oncology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada); Sahgal, Arjun [Department of Radiation Oncology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada)

    2015-11-15

    Purpose: To evaluate the applicability of the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and University of Texas MD Anderson (MDA) Cancer Center criteria in the setting of stereotactic body radiation therapy (SBRT) to nonspine bone metastases. Methods: Patients who were treated with SBRT to nonspine bone metastases were identified by retrospective chart review. An independent musculoskeletal radiologist evaluated response to treatment using computed tomography (CT) scans. Results: Thirty-three patients were treated to 42 nonspine bone metastases. The most common primary cancer cites were renal cell carcinoma (RCC) (33.3%), lung (24.2%), and prostate (18.2%). Bone metastases were either mainly lytic (57.1%), mainly sclerotic (28.6%), or mixed (14.3%). When lytic and sclerotic lesions were evaluated according to RECIST 1.1, local control (LC) was 83%, 85%, 88%, and 80% for those with CT imaging between months 1 to 3, 4 to 6, 7 to 9, and 10 to 12, respectively. When evaluated by the MDA criteria by density, LC within each time period was slightly greater. Overall LC decreased considerably when evaluated by MDA in terms of size. Conclusions: Consensus definitions of response are required as they have implications on clinical trials and disease management. Without consistent response criteria, outcomes from clinical trials cannot be compared and treatment efficacy remains undetermined.

  11. Prostate Cancer Skeletal Metastases: Pathobiology and Interventions

    Science.gov (United States)

    2005-02-01

    by vitamin D, bone morphogenetic protein-2, and cytokines. Biochem Biophys Res Commun 1998;250(3):776-78 I. [20] Hofbauer LC, Heufelder AE...cancellous bone but not in osteoarthritis . J Bone Miner Res 2001; 16(6): 1015-1027. Mechanisms of Bone Resorption in Prostate Cancer Skeletal...Costantini F. Interleukin-6 deficient mice are protected from bone loss caused by estrogen depletion. EMBO Journal 1994; 13(5):1 189-1196. [69] de

  12. Receptor conversion in distant breast cancer metastases

    NARCIS (Netherlands)

    Hoefnagel, Laurien D. C.; van de Vijver, Marc J.; van Slooten, Henk-Jan; Wesseling, Pieter; Wesseling, Jelle; Westenend, Pieter J.; Bart, Joost; Seldenrijk, Cornelis A.; Nagtegaal, Iris D.; Oudejans, Joost; van der Valk, Paul; van der Groep, Petra; de Vries, Elisabeth G. E.; van der Wall, Elsken; van Diest, Paul J.

    2010-01-01

    Introduction: When breast cancer patients develop distant metastases, the choice of systemic treatment is usually based on tissue characteristics of the primary tumor as determined by immunohistochemistry (IHC) and/or molecular analysis. Several previous studies have shown that the immunophenotype

  13. Targeting RANKL in the management of bone loss in patient with breast cancer

    National Research Council Canada - National Science Library

    Nicolin, Vanessa; Valentini, Roberto

    2014-01-01

    .... RANKL in bone has also been shown to serve as a chemoattractant for cancer cells, thu explaining the tropism of certain cancers such as breast and prostate cancer to preferentially metastasize to bone...

  14. Comparison of hybrid {sup 68}Ga-PSMA PET/MRI and {sup 68}Ga-PSMA PET/CT in the evaluation of lymph node and bone metastases of prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Freitag, Martin T.; Roethke, Matthias; Schlemmer, Heinz-Peter [German Cancer Research Center, Department of Radiology, Heidelberg (Germany); Radtke, Jan P. [German Cancer Research Center, Department of Radiology, Heidelberg (Germany); University Hospital Heidelberg, Department of Urology, Heidelberg (Germany); Hadaschik, Boris A. [University Hospital Heidelberg, Department of Urology, Heidelberg (Germany); Kopp-Schneider, A. [German Cancer Research Center, Department of Bioinformatics and Statistics, Heidelberg (Germany); Eder, Matthias; Kopka, Klaus [German Cancer Research Center, Division of Radiopharmaceutical Chemistry, Heidelberg (Germany); Haberkorn, Uwe [University Hospital Heidelberg, Department of Nuclear Medicine, Heidelberg (Germany); German Cancer Research Center, Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany); Afshar-Oromieh, Ali [University Hospital Heidelberg, Department of Nuclear Medicine, Heidelberg (Germany)

    2016-01-15

    To evaluate the reproducibility of the combination of hybrid PET/MRI and the {sup 68}Ga-PSMA-11 tracer in depicting lymph node (LN) and bone metastases of prostate cancer (PC) in comparison with that of PET/CT. A retrospective analysis of 26 patients who were subjected to {sup 68}Ga-PSMA PET/CT{sub low-dose} (1 h after injection) followed by PET/MRI (3 h after injection) was performed. MRI sequences included T1-w native, T1-w contrast-enhanced, T2-w fat-saturated and diffusion-weighted sequences (DWI{sub b800}). Discordant PET-positive and morphological findings were evaluated. Standardized uptake values (SUV) of PET-positive LNs and bone lesions were quantified and their morphological size and conspicuity determined. Comparing the PET components, the proportion of discordant PSMA-positive suspicious findings was very low (98.5 % of 64 LNs concordant, 100 % of 28 bone lesions concordant). Two PET-positive bone metastases could not be confirmed morphologically using CT{sub low-dose}, but could be confirmed using MRI. In 12 of 20 patients, 47 PET-positive LNs (71.9 %) were smaller than 1 cm in short axis diameter. There were significant linear correlations between PET/MRI SUVs and PET/CT SUVs in the 64 LN metastases (p < 0.0001) and in the 28 osseous metastases (p < 0.0001) for SUV{sub mean} and SUV{sub max}, respectively. The LN SUVs were significantly higher on PET/MRI than on PET/CT (p{sub SUVmax} < 0.0001; p{sub SUVmean} < 0.0001) but there was no significant difference between the bone lesion SUVs (p{sub SUVmax} = 0.495; p{sub SUVmean} = 0.381). Visibility of LNs was significantly higher on MRI using the T1-w contrast-enhanced fat-saturated sequence (p = 0.013), the T2-w fat-saturated sequence (p < 0.0001) and the DWI sequence (p < 0.0001) compared with CT{sub low-dose}. For bone lesions, only the overall conspicuity was higher on MRI compared with CT{sub low-dose} (p < 0.006). Nodal and osseous metastases of PC are accurately and reliably depicted by hybrid PET

  15. Bisphosphonates in oncology: evidence for the prevention of skeletal events in patients with bone metastases

    Directory of Open Access Journals (Sweden)

    Thomas J Polascik

    2008-12-01

    Full Text Available Thomas J PolascikDivision of Urology, Department of Surgery, Duke University Medical Center, Durham, NC, USAAbstract: Bone metastases frequently occur in patients with advanced solid tumors, particularly breast and prostate cancers, and nearly all patients with multiple myeloma have some degree of skeletal involvement. The strides made in treating these primary tumors have extended median survival times and thereby increased patient risk for skeletal-related events (SREs, including pathologic fractures, spinal cord compression, need for palliative radiation therapy or surgery to bone, and hypercalcemia. Bisphosphonates, inhibitors of osteoclastic bone resorption that were first established as treatment of osteoporosis, have been shown to prevent and/or delay SREs related to malignancy. The results of a large, randomized phase 3 study comparing zoledronic acid and pamidronate in breast cancer or multiple myeloma patients with osteolytic lesions showed that the incidence of SREs, time to first SRE, and risk of developing a SRE were similar between treatment groups. However, in patients with solid tumors (excluding breast or prostate cancer metastatic to the bone, only zoledronic acid has demonstrated clinical efficacy. Although bone turnover marker levels, such as N-telopeptide of type I collagen, have been shown to correlate with clinical response, additional studies are needed to validate their ability to predict response to bisphosphonate therapy.Keywords: bisphosphonates, prevention, skeletal-related events, bone metastases, cancer

  16. Cost-Effectiveness of Treatments for the Management of Bone Metastases: A Systematic Literature Review.

    Science.gov (United States)

    Andronis, Lazaros; Goranitis, Ilias; Bayliss, Sue; Duarte, Rui

    2017-12-09

    Metastatic cancers occur when cancer cells break away from the primary tumour. One of the most common sites of metastasis is the bone, with several therapeutic options currently available for managing bone metastases. In a resource-constrained environment, policy makers and practitioners need to know which options are cost effective. The aim of this systematic review was to review and appraise published economic evaluations on treatments for the management of bone metastases. We searched eight bibliographic databases (MEDLINE, MEDLINE in Process, EMBASE, CSDR, DARE, HTA, EED and CPCI) for relevant economic evaluations published from each database's inception date until March 2017. Study selection, quality assessment and data extraction were carried out according to published guidelines. Twenty-four relevant economic analyses were identified. Seventeen of these studies focused on bone metastases resulting from a particular type of cancer, i.e. prostate (n = 8), breast (n = 7), lung (n = 1) or renal (n = 1), while seven report results for various primary tumours. Across types of cancer, evidence suggests that bisphosphonates result in lower morbidity and improved quality of life, for an additional cost, which is typically below conventional cost-effectiveness thresholds. While denosumab leads to health gains compared with zoledronic acid, it also results in substantial additional costs and is unlikely to represent value for money. The limited literature on the radiopharmaceutical strontium-89 (Sr89) and external beam radiotherapy (EBR) suggest that these treatments are cost effective compared with no treatment. The reviewed evidence suggests that bisphosphonate treatments are cost-effective options for bone metastases, while denosumab is unlikely to represent value for money. Evidence on EBR and Sr89 is limited and less conclusive.

  17. Osthole inhibits bone metastasis of breast cancer.

    Science.gov (United States)

    Wu, Chunyu; Sun, Zhenping; Guo, Baofeng; Ye, Yiyi; Han, Xianghui; Qin, Yuenong; Liu, Sheng

    2017-08-29

    Bone is one of the most common sites for breast cancer metastasis, which greatly contributes to patient morbidity and mortality. Osthole, a major extract from Cnidium monnieri (L.), exhibits many biological and pharmacological activities, however, its potential as a therapeutic agent in the treatment of breast cancer bone metastases remain poorly understood. In this study, we set out to investigate whether osthole could inhibit breast cancer metastasis to bone in mice and clarified the potential mechanism of this inhibition. In the murine model of breast cancer osseous metastasis, mice that received osthole developed significantly less bone metastases and displayed decreased tumor burden when compared with mice in the control group. Osthole inhibited breast cancer cell growth, migration, and invasion, and induced apoptosis of breast cancer cells. Additionally, it also regulated OPG/RANKL signals in the interactions between bone cells (osteoblasts and osteoclasts) and cancer cells. Besides, it also inhibited TGF-β/Smads signaling in breast cancer metastasis to bone in MDA-231BO cells. The results of this study suggest that osthole has real potential as a therapeutic candidate in the treatment of breast cancer patients with bone metastases.

  18. Novel modeling of cancer cell signaling pathways enables systematic drug repositioning for distinct breast cancer metastases.

    Science.gov (United States)

    Zhao, Hong; Jin, Guangxu; Cui, Kemi; Ren, Ding; Liu, Timothy; Chen, Peikai; Wong, Solomon; Li, Fuhai; Fan, Yubo; Rodriguez, Angel; Chang, Jenny; Wong, Stephen T C

    2013-10-15

    A new type of signaling network element, called cancer signaling bridges (CSB), has been shown to have the potential for systematic and fast-tracked drug repositioning. On the basis of CSBs, we developed a computational model to derive specific downstream signaling pathways that reveal previously unknown target-disease connections and new mechanisms for specific cancer subtypes. The model enables us to reposition drugs based on available patient gene expression data. We applied this model to repurpose known or shelved drugs for brain, lung, and bone metastases of breast cancer with the hypothesis that cancer subtypes have their own specific signaling mechanisms. To test the hypothesis, we addressed specific CSBs for each metastasis that satisfy (i) CSB proteins are activated by the maximal number of enriched signaling pathways specific to a given metastasis, and (ii) CSB proteins are involved in the most differential expressed coding genes specific to each breast cancer metastasis. The identified signaling networks for the three types of breast cancer metastases contain 31, 15, and 18 proteins and are used to reposition 15, 9, and 2 drug candidates for the brain, lung, and bone metastases. We conducted both in vitro and in vivo preclinical experiments as well as analysis on patient tumor specimens to evaluate the targets and repositioned drugs. Of special note, we found that the Food and Drug Administration-approved drugs, sunitinib and dasatinib, prohibit brain metastases derived from breast cancer, addressing one particularly challenging aspect of this disease. ©2013 AACR.

  19. How Effective Are Clinical Pathways With and Without Online Peer-Review? An Analysis of Bone Metastases Pathway in a Large, Integrated National Cancer Institute-Designated Comprehensive Cancer Center Network

    Energy Technology Data Exchange (ETDEWEB)

    Beriwal, Sushil, E-mail: beriwals@upmc.edu [Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA (United States); Rajagopalan, Malolan S.; Flickinger, John C.; Rakfal, Susan M. [Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA (United States); Rodgers, Edwin [Via Oncology, Pittsburgh, PA (United States); Heron, Dwight E. [Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA (United States)

    2012-07-15

    Purpose: Clinical pathways are an important tool used to manage the quality in health care by standardizing processes. This study evaluated the impact of the implementation of a peer-reviewed clinical pathway in a large, integrated National Cancer Institute-Designated Comprehensive Cancer Center Network. Methods: In 2003, we implemented a clinical pathway for the management of bone metastases with palliative radiation therapy. In 2009, we required the entry of management decisions into an online tool that records pathway choices. The pathway specified 1 or 5 fractions for symptomatic bone metastases with the option of 10-14 fractions for certain clinical situations. The data were obtained from 13 integrated sites (3 central academic, 10 community locations) from 2003 through 2010. Results: In this study, 7905 sites were treated with 64% of courses delivered in community practice and 36% in academic locations. Academic practices were more likely than community practices to treat with 1-5 fractions (63% vs. 23%; p < 0.0001). The number of delivered fractions decreased gradually from 2003 to 2010 for both academic and community practices (p < 0.0001); however, greater numbers of fractions were selected more often in community practices (p < 0.0001). Using multivariate logistic regression, we found that a significantly greater selection of 1-5 fractions developed after implementation online pathway monitoring (2009) with an odds ratio of 1.2 (confidence interval, 1.1-1.4) for community and 1.3 (confidence interval, 1.1-1.6) for academic practices. The mean number of fractions also decreased after online peer review from 6.3 to 6.0 for academic (p = 0.07) and 9.4 to 9.0 for community practices (p < 0.0001). Conclusion: This is one of the first studies to examine the efficacy of a clinical pathway for radiation oncology in an integrated cancer network. Clinical pathway implementation appears to be effective in changing patterns of care, particularly with online clinical

  20. Skeletal Metastases Presenting as Superscan on Technetium 99m Methylene Diphosphonate Whole Body Bone Scintigraphy in Different Type of Cancers: A 5-Year Retro-prospective Study.

    Science.gov (United States)

    Manohar, P Ram; Rather, Tanveer A; Khan, Shoukat H; Malik, Dharmender

    2017-01-01

    The purpose of the study is to find out the overall incidence of superscan among different type of cancers, causes of superscan and its relationship with other parameters such as age, sex, duration of disease, and serum alkaline phosphatase (ALP) levels. This was a retro-prospective study. Records of all previous bone scans and reported patients of superscan were re-evaluated retrospectively. Patients who were diagnosed as having superscan in the preceding 3 years with confirmed histopathological diagnosis were included in the retrospective group. In the prospective group, all the patients who were reported to have superscan appearance over the past 2 years of prospective period were included. Total of 6027 bone scans were examined in a 5-year period and out of which 80 cases were diagnosed as superscan. The overall incidence of superscan in different type of cancers was 1.3% (80/6027). Prostate cancer (46/80) was the most common cause of superscan appearance followed by breast cancer (10/80). Out of 6027 patients referred for bone scan, 307 patients had prostate cancer on histopathological examination. Out of 307 patients with prostate cancer, 46 had superscan appearance. Incidence of superscan in prostate cancer was 14.98% (46/307), and 71.73% (33/46) prostate cancer patients with superscan had Gleason score of 8 and above 8 with mean serum prostate-specific antigen level was 178.42 ng/ml in symptomatic patients and 122 ng/ml in asymptomatic patients. Out of all patients with superscan, 71 patients (88.7%) had elevated serum ALP levels. Overall incidence of superscan in our study was 1.3% in different type of cancer patients, and the most common cause of superscan appearance was prostate cancer. Incidence of superscan appearance in prostatic cancer patients was 14.98%.

  1. Bone Metastasis

    Science.gov (United States)

    ... help reduce pain and other symptoms of bone metastases. Symptoms Sometimes, bone metastasis causes no signs and ... cancers most likely to cause bone metastasis include: Breast cancer Kidney cancer Lung cancer Lymphoma Multiple myeloma Prostate ...

  2. Multiple metastases from ovarian cancer

    African Journals Online (AJOL)

    Epithelial ovarian cancer is one of the most common ovarian tumours. Ovarian cancer affects women in the age group >60 years much more frequently than younger women. At the time of diagnosis, cancer will already have spread beyond the ovaries in approximately 75% of cases. We report a case of epithelial ovarian ...

  3. Cancer metastases: challenges and opportunities

    Directory of Open Access Journals (Sweden)

    Xiangming Guan

    2015-09-01

    Full Text Available Cancer metastasis is the major cause of cancer morbidity and mortality, and accounts for about 90% of cancer deaths. Although cancer survival rate has been significantly improved over the years, the improvement is primarily due to early diagnosis and cancer growth inhibition. Limited progress has been made in the treatment of cancer metastasis due to various factors. Current treatments for cancer metastasis are mainly chemotherapy and radiotherapy, though the new generation anti-cancer drugs (predominantly neutralizing antibodies for growth factors and small molecule kinase inhibitors do have the effects on cancer metastasis in addition to their effects on cancer growth. Cancer metastasis begins with detachment of metastatic cells from the primary tumor, travel of the cells to different sites through blood/lymphatic vessels, settlement and growth of the cells at a distal site. During the process, metastatic cells go through detachment, migration, invasion and adhesion. These four essential, metastatic steps are inter-related and affected by multi-biochemical events and parameters. Additionally, it is known that tumor microenvironment (such as extracellular matrix structure, growth factors, chemokines, matrix metalloproteinases plays a significant role in cancer metastasis. The biochemical events and parameters involved in the metastatic process and tumor microenvironment have been targeted or can be potential targets for metastasis prevention and inhibition. This review provides an overview of these metastasis essential steps, related biochemical factors, and targets for intervention.

  4. Cytogenetic findings in metastases from colorectal cancer

    DEFF Research Database (Denmark)

    Bardi, G; Parada, L A; Bomme, L

    1997-01-01

    Eighteen tumor samples from 11 patients with metastatic colorectal cancer were cytogenetically analyzed after short-term culturing. Of the 13 metastases examined, 11 were from lymph nodes, 1 from the peritoneum and 1 from the lung. In 5 of the 11 patients, matched samples from the primary tumor...... colorectal carcinomas, and del(10)(q22) and add(16)(p13), which so far have not been associated with primary tumors and which may play a particular pathogenetic role in the metastatic process....

  5. Breast cancer subtypes predispose the site of distant metastases.

    Science.gov (United States)

    Soni, Abha; Ren, Zhiyong; Hameed, Omar; Chanda, Diptiman; Morgan, Charity J; Siegal, Gene P; Wei, Shi

    2015-04-01

    The distant organs to which breast cancer preferentially metastasizes are of significant clinical importance. We explored the relationship between the clinicopathologic factors and the common sites of distant metastasis in 531 consecutive patients with advanced breast cancer. Breast cancer subtype as a variable was significantly associated with all five common sites of relapse by multivariate analysis. The luminal tumors were remarkable for their significant bone-seeking phenotype and were less frequently observed in lung, brain, and pleural metastases and less likely to be associated with multiorgan relapse. The HER2 subtype demonstrated a significant liver-homing characteristic. African Americans were significantly less likely to have brain-only metastasis in patients with brain relapse. These findings further articulate that breast cancer subtypes differ not only in tumor characteristics but also in their metastatic behavior, thus raising the possibility that this knowledge could potentially be used in determining the appropriate strategy for follow-up of patients with newly diagnosed breast cancer. Copyright© by the American Society for Clinical Pathology.

  6. [Management of spinal metastases of lung cancer].

    Science.gov (United States)

    La Combe, B; Gaillard, S; Bennis, S; Chouaid, C

    2013-06-01

    Spinal metastases of lung cancer occur frequently and lead to the risk of spinal cord compression. Our objective is to clarify the management of this disease, emphasizing, in particular the use of prognostic scores. The first step is to evaluate the characteristics of the spinal lesion and its impact on the autonomy and quality of life of the patient. A clinical examination is complemented by imaging procedures, such as X-rays, MRI of the spine, and PET scanning. The precise characterization of the spinal lesion permits the calculation of a predictive score for mechanical stability. The characteristics of the disease (number of metastatic sites, therapeutic possibilities, co-morbidities) can be used in decision-making. The use of prognostic scores is recommended by the Global Spine Tumour Study Group (GSTSG) for the management of spinal metastases. Among these scores, the most used are the Tokuhashi index, and the Tomita classification. They help to identify the treatment modalities, sometimes combined that might be used in the management: surgery, vertebral resection, tumour embolisation, radiotherapy, chemotherapy. The management of spinal metastases of lung cancer should be multidisciplinary. Use of prognostic scores should be encouraged to identify optimal management. Copyright © 2013 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  7. The effect of distant metastases sites on survival in de novo stage-IV breast cancer: A SEER database analysis.

    Science.gov (United States)

    Wu, San-Gang; Li, Hui; Tang, Li-Ying; Sun, Jia-Yuan; Zhang, Wen-Wen; Li, Feng-Yan; Chen, Yong-Xiong; He, Zhen-Yu

    2017-06-01

    To investigate the effect of distant metastases sites on survival in patients with de novo stage-IV breast cancer. From 2010 to 2013, patients with a diagnosis of de novo stage-IV breast cancer were identified using the Surveillance, Epidemiology, and End Results database. Univariate and multivariate Cox regression analyses were performed to analyze the effect of distant metastases sites on breast cancer-specific survival and overall survival. A total of 7575 patients were identified. The most common metastatic sites were bone, followed by lung, liver, and brain. Patients with hormone receptor+/human epidermal growth factor receptor 2- and hormone receptor+/human epidermal growth factor receptor 2+ status were more prone to bone metastases. Lung and brain metastases were common in hormone receptor-/human epidermal growth factor receptor 2+ and hormone receptor-/human epidermal growth factor receptor 2- subtypes, and patients with hormone receptor+/ human epidermal growth factor receptor 2+ and hormone receptor-/human epidermal growth factor receptor 2+ subtypes were more prone to liver metastases. Patients with liver and brain metastases had unfavorable prognosis for breast cancer-specific survival and overall survival, whereas bone and lung metastases had no effect on patient survival in multivariate analyses. The hormone receptor-/human epidermal growth factor receptor 2- subtype conferred a significantly poorer outcome in terms of breast cancer-specific survival and overall survival. hormone receptor+/human epidermal growth factor receptor 2+ disease was associated with the best prognosis in terms of breast cancer-specific survival and overall survival. Patients with liver and brain metastases were more likely to experience poor prognosis for breast cancer-specific survival and overall survival by various breast cancer subtypes. Distant metastases sites have differential impact on clinical outcomes in stage-IV breast cancer. Follow-up screening for brain and

  8. Role of denosumab in the management of skeletal complications in patients with bone metastases from solid tumors

    Directory of Open Access Journals (Sweden)

    Stopeck AT

    2012-04-01

    Full Text Available Ursa Brown-Glaberman, Alison T StopeckUniversity of Arizona Cancer Center, Tucson, AZ, USAAbstract: Skeletal-related events (SREs including pain, fractures, and hypercalcemia are a major source of morbidity for cancer patients with bone metastases. The receptor activator of NF-κB ligand (RANKL is a key mediator of osteoclast formation and activity in normal bone physiology as well as cancer-induced bone resorption. The first commercially available drug that specifically targets and inhibits the RANKL pathway is denosumab, a fully human monoclonal antibody that binds and neutralizes RANKL, thereby inhibiting osteoclast function. In this review, we summarize the major studies leading to the US Food and Drug Administration-approval of denosumab for the prevention of SREs in patients with bone metastases from solid tumors. Further, we discuss the role of denosumab in the prevention and treatment of SREs and bone loss in cancer patients. As a monoclonal antibody, denosumab has several advantages over bisphosphonates, including improved efficacy, better tolerability, and the convenience of administration by subcutaneous injection. In addition, as denosumab has no known renal toxicity, it may be the preferred choice over bisphosphonates in patients with baseline renal insufficiency or receiving nephrotoxic therapies. However, other toxicities, including osteonecrosis of the jaw and hypocalcemia, appear to be class effects of agents that potently inhibit osteoclast activity and are associated with both denosumab and bisphosphonate use. The data presented highlight the differences associated with intravenous bisphosphonate and denosumab use as well as confirm the essential role bone-modifying agents play in maintaining the quality of life for patients with bone metastases.Keywords: denosumab, bone metastases, solid tumor, breast cancer, prostate cancer, skeletal related events, skeletal complications 

  9. Patterns of Care Among Patients Receiving Radiation Therapy for Bone Metastases at a Large Academic Institution

    Energy Technology Data Exchange (ETDEWEB)

    Ellsworth, Susannah G. [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Alcorn, Sara R., E-mail: salcorn2@jhmi.edu [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Hales, Russell K.; McNutt, Todd R.; DeWeese, Theodore L. [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Smith, Thomas J. [Department of Medical Oncology and Harry J. Duffey Family Program in Palliative Care, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States)

    2014-08-01

    Purpose: This study evaluates outcomes and patterns of care among patients receiving radiation therapy (RT) for bone metastases at a high-volume academic institution. Methods and Materials: Records of all patients whose final RT course was for bone metastases from April 2007 to July 2012 were identified from electronic medical records. Chart review yielded demographic and clinical data. Rates of complicated versus uncomplicated bone metastases were not analyzed. Results: We identified 339 patients whose final RT course was for bone metastases. Of these, 52.2% were male; median age was 65 years old. The most common primary was non-small-cell lung cancer (29%). Most patients (83%) were prescribed ≤10 fractions; 8% received single-fraction RT. Most patients (52%) had a documented goals of care (GOC) discussion with their radiation oncologist; hospice referral rates were higher when patients had such discussions (66% with vs 50% without GOC discussion, P=.004). Median life expectancy after RT was 96 days. Median survival after RT was shorter based on inpatient as opposed to outpatient status at the time of consultation (35 vs 136 days, respectively, P<.001). Hospice referrals occurred for 56% of patients, with a median interval between completion of RT and hospice referral of 29 days and a median hospice stay of 22 days. Conclusions: These data document excellent adherence to American Society for Radiation Oncolology Choosing Wisely recommendation to avoid routinely using >10 fractions of palliative RT for bone metastasis. Nonetheless, single-fraction RT remains relatively uncommon. Participating in GOC discussions with a radiation oncologist is associated with higher rates of hospice referral. Inpatient status at consultation is associated with short survival.

  10. Liver resection for colorectal cancer metastases

    Science.gov (United States)

    Gallinger, S.; Biagi, J.J.; Fletcher, G.G.; Nhan, C.; Ruo, L.; McLeod, R.S.

    2013-01-01

    Questions Should surgery be considered for colorectal cancer (crc) patients who have liver metastases plus (a) pulmonary metastases, (b) portal nodal disease, or (c) other extrahepatic metastases (ehms)? What is the role of chemotherapy in the surgical management of crc with liver metastases in (a) patients with resectable disease in the liver, or (b) patients with initially unresectable disease in the liver that is downsized with chemotherapy (“conversion”)? What is the role of liver resection when one or more crc liver metastases have radiographic complete response (rcr) after chemotherapy? Perspectives Advances in chemotherapy have improved survival in crc patients with liver metastases. The 5-year survival with chemotherapy alone is typically less than 1%, although two recent studies with folfox or folfoxiri (or both) reported rates of 5%–10%. However, liver resection is the treatment that is most effective in achieving long-term survival and offering the possibility of a cure in stage iv crc patients with liver metastases. This guideline deals with the role of chemotherapy with surgery, and the role of surgery when there are liver metastases plus ehms. Because only a proportion of patients with crc metastatic disease are considered for liver resection, and because management of this patient population is complex, multidisciplinary management is required. Methodology Recommendations in the present guideline were formulated based on a prepublication version of a recent systematic review on this topic. The draft methodology experts, and external review by clinical practitioners. Feedback was incorporated into the final version of the guideline. Practice Guideline These recommendations apply to patients with liver metastases from crc who have had or will have a complete (R0) resection of the primary cancer and who are being considered for resection of the liver, or liver plus specific and limited ehms, with curative intent. 1(a). Patients with liver and lung

  11. Clinical Characteristics of Lung Cancer with Pancreatic Metastases

    Directory of Open Access Journals (Sweden)

    Jianchun DUAN

    2017-08-01

    Full Text Available Background and objective Lacking of typical symptoms, more than 70% of patients with lung cancer are diagnosed as advanced-stage disease. Patients suffer from solid organs metastasis with different clinical features and prognosis. With development of new technology, more and more lung cancer patients are diagnosed with pancreatic metastasis. The aim of this study was to investigate clinicopathologic and survival difference by retrospective analysis among lung cancer patients with pancreatic metastases. Methods Of the patients with lung cancer diagnosed by pathology and thorough staging evaluation and treated at Beijing Cancer Hospital with long follow-up during July 1996 and June 2017, 35 cases had pancreatic metastases. Results There were 28 cases diagnosed as small cell lung cancer, 3 cases diagnosed as adenocarcinoma and 4 cases diagnosed as squamous cell carcinoma. There were 15 cases with pancreatic metastases in head of pancreas and 20 cases in body and tail of pancreas, 23 cases presented with isolated metastasis and 12 cases with multiple metastases. Pathological type was prognostic factor for lung cancer patients with pancreatic metastases. Conclusion Pancreatic metastases represents an uncommon site of extrathoracic spread of disease for part of patients with advanced lung cancer. Lung cancer with pancreatic metastases should be treated by combined therapy, especially by systemic chemotherapy. Pathological type was prognostic factor for lung cancer patients with pancreatic metastases.

  12. Attributes of brain metastases from breast and lung cancer.

    Science.gov (United States)

    Hengel, Kyle; Sidhu, Gurinder; Choi, Jai; Weedon, Jeremy; Nwokedi, Emmanuel; Axiotis, Constantine A; Song, Xianyuan; Braverman, Albert S

    2013-06-01

    Most brain metastases arise from breast and lung cancers. Few studies compare the brain regions they involve, their numbers and intrinsic attributes. Records of all patients referred to Radiation Oncology for treatment of symptomatic brain metastases were obtained. Computed tomography (n = 56) or magnetic resonance imaging (n = 72) brain scans were reviewed. Data from 68 breast and 62 lung cancer patients were compared. Brain metastases presented earlier in the course of the lung than of the breast cancer patients (p = 0.001). There were more metastases in the cerebral hemispheres of the breast than of the lung cancer patients (p = 0.014). More breast than lung cancer patients had cerebellar metastases (p = 0.001). The number of cerebral hemisphere metastases and presence of cerebellar metastases were positively correlated (p = 0.001). The prevalence of at least one metastasis surrounded with >2 cm of edema was greater for the lung than for the breast patients (p = 0.019). The primary tumor type, rather than the scanning method, correlated with differences between these variables. Brain metastases from lung occur earlier, are more edematous, but fewer in number than those from breast cancers. Cerebellar brain metastases are more frequent in breast cancer.

  13. Influence of the location and number of metastases in the survival of metastatic prostatic cancer patients.

    Science.gov (United States)

    Guijarro, A; Hernández, V; de la Morena, J M; Jiménez-Valladolid, I; Pérez-Fernández, E; de la Peña, E; Llorente, C

    2017-05-01

    The prognosis of patients diagnosed with metastatic prostate cancer seems to be modulated by factors such as the number and site of metastases. Our objective is to evaluate survival outcomes according to the number and site of metastases in our series of metastatic patients over the last 15 years. A retrospective analysis was performed on patients diagnosed between 1998 and 2014. We analyzed overall survival and progression-free survival, depending on the number and location of metastases on patients with newly diagnosed metastatic prostate cancer. Other potential prognostic factors were also evaluated: age, clinical stage, PSA at diagnosis, Gleason, PSA nadir, time till PSA nadir and first-line or second-line treatment after progression. We analyzed a series of 162 patients. The mean age was 72.7yr (SD: 8.5). The estimated median overall survival was 3.9 yr (95% CI 2.6-5.2). The overall survival in patients with only lymph node metastases was 7 yr (95% CI 4.1-9.7), 3.9 (95%CI 2.3-5.5) in patients with only bone metastases, 2.5 yr (95% CI 2-2.3) in lymph nodes and bone metastases, and 2.2 yr (95% CI 1.4-3) in patients with visceral metastases (Pnumber of metastases showed no association with survival. The site of metastases has a clear impact on both overall survival and progression-free survival. Patients with only lymph node involvement had a better prognosis. The number of metastases showed no significant impact on survival in our series. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  14. Efficacy and safety of radium-223 dichloride in patients with castration-resistant prostate cancer and symptomatic bone metastases, with or without previous docetaxel use: a prespecified subgroup analysis from the randomised, double-blind, phase 3 ALSYMPCA trial.

    Science.gov (United States)

    Hoskin, Peter; Sartor, Oliver; O'Sullivan, Joe M; Johannessen, Dag Clement; Helle, Svein I; Logue, John; Bottomley, David; Nilsson, Sten; Vogelzang, Nicholas J; Fang, Fang; Wahba, Mona; Aksnes, Anne-Kirsti; Parker, Christopher

    2014-11-01

    Primary results from the phase 3 ALSYMPCA trial showed that radium-223 dichloride (radium-223), a targeted α-emitter, improved overall survival compared with placebo and was well tolerated in patients with castration-resistant prostate cancer and symptomatic bone metastases. We did a prespecified subgroup analysis from ALSYMPCA to assess the effect of previous docetaxel use on the efficacy and safety of radium-223. In the phase 3, randomised, double-blind ALSYMPCA trial, patients with symptomatic castration-resistant prostate cancer, at least two symptomatic bone metastases, no known visceral metastases, and who were receiving best standard of care were randomly assigned (2:1) via an interactive voice response system to receive six injections of radium-223 (50 kBq/kg intravenously) or matching placebo, with one injection given every 4 weeks. Patients had either received previous docetaxel treatment or were unsuitable for or declined docetaxel; previous docetaxel use (yes or no) was a trial stratification factor. We investigated the effect of previous docetaxel use on radium-223 treatment for the primary endpoint of overall survival, the main secondary efficacy endpoints, and safety. Efficacy analyses were done for the intention-to-treat population; safety analyses were done for the safety population. The trial has been completed and is registered with ClinicalTrials.gov, number NCT00699751. Randomisation took place between June 12, 2008, and Feb 1, 2011. 526 (57%) of 921 randomly assigned patients had received previous docetaxel treatment (352 in the radium-223 group and 174 in the placebo group) and 395 (43%) had not (262 in the radium-223 group and 133 in the placebo group). Radium-223 prolonged median overall survival compared with placebo, irrespective of previous docetaxel use (previous docetaxel use, hazard ratio [HR] 0·70, 95% CI 0·56-0·88; p=0·002; no previous docetaxel use, HR 0·69, 0·52-0·92; p=0·01). The benefit of radium-223 compared with

  15. Cementoplasty for managing painful bone metastases outside the spine

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Gang; Jin, Peng; Liu, Xun-wei; Li, Min; Li, Li [Jinan Military General Hospital, Department of Medical Imaging, Jinan, Shandong Province (China)

    2014-03-15

    To illustrate the effect of treatment with cementoplasty in patients with painful bone metastases in the extraspinal region. A retrospective study was conducted to review 51 consecutive patients who underwent cementoplasty under CT or fluoroscopic guidance, a total of 65 lesions involving the ilium, ischium, pubis, acetabulum, humeral, femur and tibia. In 5 patients with a high risk of impending fracture in long bones based on Mirels' scoring system, an innovative technique using a cement-filled catheter was applied. The clinical effects were evaluated using the visual analogue scale (VAS) preoperatively and postoperatively. All patients were treated successfully with a satisfying resolution of painful symptoms at 3 months' follow-up. Cement leakage was found in 8 lesions without any symptoms. VAS scores decreased from 8.19 ± 1.1 preoperatively to 4.94 ± 1.6 at 3 days, 3.41 ± 2.1 at 1 month and 3.02 ± 1.9 at 3 months postoperatively. There was a significant difference between the mean preoperative baseline score and the mean score at all of the postoperative follow-up points (P < 0.01). Cementoplasty is an effective technique for treating painful bone metastases in extraspinal regions, which is a valuable, minimally invasive, method that allows reduction of pain and improvement of patients' quality of life. (orig.)

  16. Bone health in patients with prostate cancer.

    Science.gov (United States)

    Miñana, B; Cózar, J M; Alcaraz, A; Morote, J; Gómez-Veiga, F J; Solsona, E; Rodríguez-Antolín, A; Carballido, J

    2014-12-01

    In patients with prostate cancer, bone health is compromised by advanced age at diagnosis, androgen suppression treatments and the developmentofbone metastases. In this paper the medical literature is reviewed in order to update the state of the art on their incidence, prevention and management. A literature review about bone involvement in patients with prostate cancer in different clinical settings is performed. Decreased bone mineral density is higher in patients diagnosed of prostate cancer before starting treatment than in healthy men with the same age. During the first year of treatment, a severe loss bone density is reported due to androgen suppression therapy. From then on, loss bone density seems to slow down, persisting at long-term. It is important to know the starting point and the dynamics of loss bone in order to prevent its progression. The skeletal events have an important impact on quality of life in patients with prostate cancer. Both Denosumab and Zoledronic Acid have proven effective in reducing loss bone. The prevention and management of bone involvement in patients with prostate cancer is critical to quality of life in these patients and requires an individualized approach. Before starting a prolonged androgen deprivation, baseline risk of fracture should be evaluated in order to adopt the proper protective measures. In patients with metastases, early treatments reducing the risk of bone events should be taken into account. Copyright © 2014 AEU. Published by Elsevier Espana. All rights reserved.

  17. Diagnostic Value of Technetium-99m Bone Scintigraphy in the Detection of Cervical Spine Metastases in Oncological Patients.

    Science.gov (United States)

    Park, Sang-Min; Park, Jae-Woo; Lee, Hui-Jong; Choi, Ja-Young; Yoo, Hye Jin; Lee, Choon-Ki; Chang, Bong-Soon; Kim, Hyoungmin

    2017-11-15

    MINI: Bone scan remains the modality of choice for the screening of bone metastases. This study demonstrated the diagnostic value of bone scan in detecting bone metastases limited to the cervical spine in oncological patients remains uncertain due to the moderately high false-negative diagnostic rate. A retrospective cohort, radiographic study. To assess the diagnostic accuracy of bone scintigraphy (BS) for the detection of cervical spine metastases in oncological patients. BS remains the modality of choice for the screening of bone metastases, because of its feasibility in whole-body scanning and its widespread availability at low cost. Current practice guidelines for patients with malignant diseases recommend BS imaging as the primary screening method for detecting both axial and appendicular skeletal metastases. Of 481 patients, 242 were diagnosed with cervical spinal metastases from a primary cancer. The BS findings of these patients, evaluated by nuclear medicine physicians, were assessed with respect to their usefulness for detecting cervical spine metastases. Magnetic resonance imaging findings, evaluated by radiologists, were used as the reference standards. The diagnostic value of BS was compared between subgroups according to the order in which the diagnostic procedures (magnetic resonance imaging and BS) were completed, the presence of pathological fractures, the location of the primary malignancy, and the number of cervical metastases. The sensitivity of BS in the detection of cervical spine metastases was 59.1%, with a 40.9% rate of false-negative diagnoses; the specificity was 94.6%, with a 5.4% rate of false-positive diagnoses. The sensitivity tended to be higher in the presence of pathological fractures (72.1% in cases with a fracture vs. 3% in cases without a fracture) and a greater number of lesions (r = 0.921). Neither the order in which the diagnostic examinations were performed nor the location of the primary cancer, except for those in the

  18. An Easy Tool to Predict Survival in Patients Receiving Radiation Therapy for Painful Bone Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Westhoff, Paulien G., E-mail: p.g.westhoff@umcutrecht.nl [Department of Radiotherapy, University Medical Center Utrecht, Utrecht (Netherlands); Graeff, Alexander de [Department of Medical Oncology, University Medical Center Utrecht, Utrecht (Netherlands); Monninkhof, Evelyn M. [Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht (Netherlands); Bollen, Laurens; Dijkstra, Sander P. [Department of Orthopedic Surgery, Leiden University Medical Center (Netherlands); Steen-Banasik, Elzbieta M. van der [ARTI Institute for Radiation Oncology Arnhem, Arnhem (Netherlands); Vulpen, Marco van [Department of Radiotherapy, University Medical Center Utrecht, Utrecht (Netherlands); Leer, Jan Willem H. [Department of Radiotherapy, University Medical Center Nijmegen, Nijmegen (Netherlands); Marijnen, Corrie A.; Linden, Yvette M. van der [Department of Clinical Oncology, Leiden University Medical Center, Leiden (Netherlands)

    2014-11-15

    Purpose: Patients with bone metastases have a widely varying survival. A reliable estimation of survival is needed for appropriate treatment strategies. Our goal was to assess the value of simple prognostic factors, namely, patient and tumor characteristics, Karnofsky performance status (KPS), and patient-reported scores of pain and quality of life, to predict survival in patients with painful bone metastases. Methods and Materials: In the Dutch Bone Metastasis Study, 1157 patients were treated with radiation therapy for painful bone metastases. At randomization, physicians determined the KPS; patients rated general health on a visual analogue scale (VAS-gh), valuation of life on a verbal rating scale (VRS-vl) and pain intensity. To assess the predictive value of the variables, we used multivariate Cox proportional hazard analyses and C-statistics for discriminative value. Of the final model, calibration was assessed. External validation was performed on a dataset of 934 patients who were treated with radiation therapy for vertebral metastases. Results: Patients had mainly breast (39%), prostate (23%), or lung cancer (25%). After a maximum of 142 weeks' follow-up, 74% of patients had died. The best predictive model included sex, primary tumor, visceral metastases, KPS, VAS-gh, and VRS-vl (C-statistic = 0.72, 95% CI = 0.70-0.74). A reduced model, with only KPS and primary tumor, showed comparable discriminative capacity (C-statistic = 0.71, 95% CI = 0.69-0.72). External validation showed a C-statistic of 0.72 (95% CI = 0.70-0.73). Calibration of the derivation and the validation dataset showed underestimation of survival. Conclusion: In predicting survival in patients with painful bone metastases, KPS combined with primary tumor was comparable to a more complex model. Considering the amount of variables in complex models and the additional burden on patients, the simple model is preferred for daily use. In addition, a risk table for survival is

  19. Soft tissue metastases from differentiated thyroid cancer diagnosed by {sup 18}F FDG PET-CT

    Energy Technology Data Exchange (ETDEWEB)

    Califano, Ines; Quildrian, Sergio; Otero, Jose; Coduti, Martin; Califano, Leonardo; Rojas Bilbao, Erica, E-mail: ines.m.califano@gmail.com [Instituto de Oncologia Angel H. Roffo, Universidad de Buenos Aires (Argentina)

    2013-06-15

    Distant metastases of differentiated thyroid cancer are unusual; lung and bones are the most frequently affected sites. Soft tissue metastases (STM) are extremely rare. We describe two cases of patients with differentiated thyroid cancer metastasizing to soft tissues. Both patients had widespread metastatic disease; clinically asymptomatic soft tissue metastases were found by 18-Fluorodeoxyglucose positron emission tomography/computed tomography ({sup 18}F FDG PET-CT), and confirmed by cytological and/or histopathological studies. These findings underscore the ability of {sup 18}F FDG PET-CT in accurately assessing the extent of the disease, as well as the utility of the method to evaluate regions of the body that are not routinely explored. (author)

  20. Cause of death from liver metastases in colorectal cancer.

    Science.gov (United States)

    Helling, Thomas S; Martin, Magdeline

    2014-02-01

    Surgically directed therapy for liver metastases from colorectal cancer (CRC) has received substantial attention in the literature as a major focus of treatment for metastatic CRC. It is presumed, but not proven, that liver metastases are a major threat to life. This study examined the course of a cohort of consecutive patients who died with CRC to determine the role played by the presence of liver metastases. This is single-institution retrospective observational study involved all patients who died of CRC. Records were examined and imaging studies reviewed to determine the extent of liver and extrahepatic metastases in these patients. Overall survival in patients with and without liver metastases and those in whom liver metastases were thought to contribute to death was determined. After patient exclusions, the study population totaled 121 patients. There were 75 patients (62%) with liver metastases at death. In 40 of 75 (53%) patients, the liver metastases contributed to the patients' death. In 46 of 121 patients (38%), metastatic disease did not include liver metastases. Overall survival in patients with and without liver metastases (median survival 12 vs. 8.5 months, p = 0.089) and in those whose liver metastases did or did not contribute to death (median survival 11.5 vs. 14 months, p = 0.361) was not significant. The presence of liver metastases seemed to contribute to death in approximately half of the study patients, although there did not appear to be a survival disadvantage in these patients.

  1. Radioactive bone cement for the treatment of spinal metastases: a dosimetric analysis of simulated clinical scenarios

    Science.gov (United States)

    Kaneko, T. S.; Sehgal, V.; Skinner, H. B.; Al-Ghazi, M. S. A. L.; Ramsinghani, N. S.; Marquez Miranda, M.; Keyak, J. H.

    2012-07-01

    Vertebral metastases are a common manifestation of many cancers, potentially leading to vertebral collapse and neurological complications. Conventional treatment often involves percutaneous vertebroplasty/kyphoplasty followed by external beam radiation therapy. As a more convenient alternative, we have introduced radioactive bone cement, i.e. bone cement incorporating a radionuclide. In this study, we used a previously developed Monte Carlo radiation transport modeling method to evaluate dose distributions from phosphorus-32 radioactive cement in simulated clinical scenarios. Isodose curves were generally concentric about the surface of bone cement injected into cadaveric vertebrae, indicating that dose distributions are relatively predictable, thus facilitating treatment planning (cement formulation and dosimetry method are patent pending). Model results indicated that a therapeutic dose could be delivered to tumor/bone within ∼4 mm of the cement surface while maintaining a safe dose to radiosensitive tissue beyond this distance. This therapeutic range should be sufficient to treat target volumes within the vertebral body when tumor ablation or other techniques are used to create a cavity into which the radioactive cement can be injected. With further development, treating spinal metastases with radioactive bone cement may become a clinically useful and convenient alternative to the conventional two-step approach of percutaneous strength restoration followed by radiotherapy.

  2. The Use of Massive Endoprostheses for the Treatment of Bone Metastases

    Directory of Open Access Journals (Sweden)

    D. H. Park

    2007-01-01

    Full Text Available Purpose. We report a series of 58 patients with metastatic bone disease treated with resection and endoprosthetic reconstruction over a five-year period at our institution. Introduction. The recent advances in adjuvant and neoadjuvant therapy in cancer treatment have resulted in improved prognosis of patients with bone metastases. Most patients who have either an actual or impending pathological fracture should have operative stabilisation or reconstruction. Endoprosthetic reconstructions are indicated in patients with extensive bone loss, failed conventional reconstructions, and selected isolated metastases. Methods and Results. We identified all patients who were diagnosed with metastatic disease to bone between 1999 and 2003. One hundred and seventy-one patients were diagnosed with bone metastases. Metastatic breast and renal cancer accounted for 84 lesions (49%. Fifty-eight patients with isolated bone metastasis to the appendicular skeleton had an endoprosthetic reconstruction. There were 28 males and 30 females. Twelve patients had an endoprosthesis in the upper extremity and 46 patients had an endoprosthesis in the lower extremity. The mean age at presentation was 62 years (24 to 88. At the time of writing, 19 patients are still alive, 34 patients have died, and 5 have been lost to follow up. Patients were followed up and evaluated using the musculoskeletal society tumour score (MSTS and the Toronto extremity salvage score (TESS. The mean MSTS was 73% (57% to 90% and TESS was 71% (46% to 95%. Mean follow-up was 48.2 months (range 27 to 82 months and patients died of disease at a mean of 22 months (2 to 51 months from surgery. Complications included 5 superficial wound infections, 1 aseptic loosening, 4 dislocations, 1 subluxation, and 1 case, where the tibial component of a prosthesis rotated requiring open repositioning. Conclusions. We conclude that endoprosthetic replacement for the treatment of isolated bone metastases is a reliable

  3. Improved detection of lung or bone metastases with an I-131 whole body scan on the 7th day after high-dose I-131 therapy in patients with thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chong, Ar I; Song, Ho Chun; Min, Jung Joon; Kim, Ja Hae; Yoo, Su Ung; Oh, Jong Ryool; Bom, Hee Seung [Chonnam National University Medical School, Gwangju (Korea, Republic of); Jeong, Shin Young [Kyungpook National University Hospital, Daegu (Korea, Republic of); Ha, Jung Min [Chosun University Hospital, Gwangju (Korea, Republic of)

    2010-12-15

    The purpose of this study is to compare post-therapy third day and seventh day I-131 whole body scans (3DWBS and 7DWBS) in detecting lung or bone metastasis from well-differentiated thyroid cancer. We enrolled 52 patients with lung or bone metastasis out of 1,152 patients who were treated with high-dose I-131 therapy from January 2008 to June 2009. All patients underwent 3DWBS and 7DWBS. I-131 avidity was classified into three grades: no uptake, suspicious for uptake, and definite uptake. We compared the presence and grades of metastatic lesions on each scan. We categorized all cases into three groups based on I-131 uptake on each scan and compared several clinical parameters including FDG uptake and thyroglobulin (Tg) level among the groups. Sixty metastatic cases from 52 patients (45 lung and 15 bone metastases) were included. In 35 cases, I-131-avid metastatic lesions were detected by both 3DWBS and 7DWBS (group A). In 15 cases, metastatic lesions were missed on 3DWBS but detected on 7DWBS (group B). In 10 cases, I-131 uptake was not detected on either 3DWBS or 7DWBS (group C). The of 45 cases (22.2%) of lung metastasis that were negative on 3DWBS were detected on 7DWBS (p=0.002). Five of 15 cases (33.3%) of bone metastasis that were negative on 3DWBS were detected on 7DWBS (p=0.0625). The serum Tg level (TSH stimulated) was significantly different among groups A, B, and C (p=0.0030). However, after exclusion of cases without a history of I-131 therapy, there was no significant difference in serum Tg level among the groups (p=0.2330). The number of cases with a prior history of metastasis was higher in group A than in group B (p=0.0069). However, there was no significant difference in prior history of metastasis between groups A and C (p=0.8107). 7DWBS showed more lung or bone metastatic lesions than 3DWBS. After high-dose I-131 therapy, 7DWBS should be considered regardless of the results of the 3DWBS for the diagnosis of lung or bone metastasis from well

  4. Assessment of Bone Metastases in Patients with Prostate Cancer—A Comparison between 99mTc-Bone-Scintigraphy and [68Ga]Ga-PSMA PET/CT

    Directory of Open Access Journals (Sweden)

    Lena Thomas

    2017-07-01

    Full Text Available Purpose: Bone scintigraphy is the standard of reference in bone metastases in prostate cancer patients. However, new radiotracers employed in prostate-specific membrane antigen (PSMA-ligands has led to the growing importance of PET/CT as diagnostic tool. The aim of our study was to investigate the difference between bone scan and PSMA-PET/CT for the detection of bone metastases in prostate cancer. Methods: Thirty patients with bone metastases originating from prostate cancer were examined by 99mTc-MDP bone scan and 68Ga-PSMA-PET/CT within an average of 21 days. Bone scans were analyzed visually according to the number of lesions and using the software package ExiniBONE by Exini Diagnostics. PET/CT data was analyzed visually. Numbers of detected lesions were compared for the different methods for the whole patient and for different regions. In addition, results were compared to serum prostate-specific antigen (PSA, alkaline phosphatase (ALP, bone alkaline phosphatase (bALP, pro gastrin releasing peptide (pGRP and eastern cooperative oncology group (ECOG performance status. Results: In the bone scans, visual and semiautomatic lesion detection showed similar results with an average of 19.4 and 17.8 detected bone lesion per patient. However, in PSMA-PET/CT, on average double the numbers of lesions (40.0 were detected. The largest differences were found in the thorax and pelvis, which can be explained by the advantages of tomographic imaging. Bland-Altman analysis showed greater differences in patients with large numbers of bone metastases. Conclusion: No significant difference was found when using semiautomatic analysis compared to visual reading for bone scans. Fewer bone metastases were detected in bone scans than in PSMA-PET/CT. However, in none of our patients would the difference have led to clinical consequences. Therefore, it seems that for patients undergoing PSMA-PET/CT, there is no need to perform additional bone scans if the appropriate

  5. Quality of Life in Relation to Pain Response to Radiation Therapy for Painful Bone Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Westhoff, Paulien G., E-mail: p.g.westhoff@umcutrecht.nl [Department of Radiotherapy, University Medical Center Utrecht, Utrecht (Netherlands); Graeff, Alexander de [Department of Medical Oncology, University Medical Center Utrecht, Utrecht (Netherlands); Monninkhof, Evelyn M. [Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht (Netherlands); Pomp, Jacqueline [Department of Radiotherapy, Reinier de Graaf Gasthuis, Delft (Netherlands); Vulpen, Marco van [Department of Radiotherapy, University Medical Center Utrecht, Utrecht (Netherlands); Leer, Jan Willem H. [Department of Radiotherapy, University Medical Center Nijmegen, Nijmegen (Netherlands); Marijnen, Corrie A.M.; Linden, Yvette M. van der [Department of Clinical Oncology, Leiden University Medical Center, Leiden (Netherlands)

    2015-11-01

    Purpose: To study quality of life (QoL) in responders and nonresponders after radiation therapy for painful bone metastases; and to identify factors predictive for a pain response. Patients and Methods: The prospectively collected data of 956 patients with breast, prostate, and lung cancer within the Dutch Bone Metastasis Study were used. These patients, irradiated for painful bone metastases, rated pain, QoL, and overall health at baseline and weekly afterward for 12 weeks. Using generalized estimating equations analysis, the course of QoL was studied, adjusted for primary tumor. To identify predictive variables, proportional hazard analyses were performed, taking into account death as a competing risk, and C-statistics were calculated for discriminative value. Results: In total, 722 patients (76%) responded to radiation therapy. During follow-up, responders had a better QoL in all domains compared with nonresponders. Patients with breast or prostate cancer had a better QoL than patients with lung cancer. In multivariate analysis, baseline predictors for a pain response were breast or prostate cancer as primary tumor, younger age, good performance status, absence of visceral metastases, and using opioids. The discriminative ability of the model was low (C-statistic: 0.56). Conclusions: Responding patients show a better QoL after radiation therapy for painful bone metastases than nonresponders. Our model did not have enough discriminative power to predict which patients are likely to respond to radiation therapy. Therefore, radiation therapy should be offered to all patients with painful bone metastases, aiming to decrease pain and improve QoL.

  6. Patients' and health care professionals' evaluation of health-related quality of life issues in bone metastases.

    Science.gov (United States)

    Harris, Kristin; Chow, Edward; Zhang, Liying; Velikova, Galina; Bezjak, Andrea; Wu, Jackson; Barton, Michael; Sezer, Orhan; Eek, Richard; Shafiq, Jesmin; Yee, Albert; Clemons, Mark; Brundage, Michael; Hoskin, Peter; van der Linden, Yvette; Johnson, Colin D; Bottomley, Andrew

    2009-09-01

    The objective of this study was to examine the agreement between health care professionals' (HCPs) and patients' evaluation of health-related quality of life (HRQOL) issues for cancer patients with bone metastases. A total of 413 patients and 152 HCPs were interviewed across five centres worldwide. Mean scores were almost always higher for HCPs than for patients. Patients and HCPs agreed that four issues affect HRQOL of bone metastases patients profoundly: 'long-term (chronic) pain', 'difficulty in carrying out usual daily tasks', 'able to perform self-care' and 'able to perform role functioning'. A substantial difference was found with respect to the perceived importance of psychosocial and somatic issues. Patients emphasised psychosocial issues with a particular focus on 'worry' about loss of mobility, dependence on others and disease progression, HCPs however rated 'symptom' issues as more important, specifically those related to 'pain'. In conclusion, patients and HCPs agreed that pain and physical/role functioning are important to the HRQOL of cancer patients with bone metastases, but patients also emphasized the importance of psychosocial issues to HRQOL. This information has been an important component in the development of a health-related quality of life questionnaire for patients with bone metastases (EORTC QLQ-BM 22).

  7. From Prostate to Bone: Key Players in Prostate Cancer Bone Metastasis

    OpenAIRE

    Thobe, Megan N.; Rinker-Schaeffer, Carrie W.; Clark, Robert J.; Bainer, Russell O; Prasad, Sandip M.

    2011-01-01

    Bone is the most common site for metastasis in human prostate cancer patients. Skeletal metastases are a significant cause of morbidity and mortality and overall greatly affect the quality of life of prostate cancer patients. Despite advances in our understanding of the biology of primary prostate tumors, our knowledge of how and why secondary tumors derived from prostate cancer cells preferentially localize bone remains limited. The physiochemical properties of bone, and signaling molecules ...

  8. Evaluation of diagnostic procedures such as plain-film scintigraphy and MR imaging for spinal metastases in relation to biological characteristics in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yamashita, Hiroya; Nagao, Kazuharu; Nishimura, Reiki; Matsuda, Kazumasa; Baba, Kenichiro; Matsuoka, Yukio; Fukuda, Makoto; Higuchi, Akihiro; Saeki, Takahito [Kumamoto City Hospital (Japan)

    1995-09-01

    The relationship between spinal metastases diagnosed by plain-film, bone scintigraphy, and MR imaging and biological characteristics in 26 patients with breast cancer was investigated retrospectively. It was found that bone scintigraphy is useful for detecting metastases in case with slow-growing tumors determined by DNA polymerase {alpha} or with estrogen-receptor (ER) positivity. In contrast, cases with rapidly growing tumors showed false-negative plain-film or bone scintigraphy results, including cases with ER-negative tumors or DNA polymerase {alpha} of more than 20%. MR imaging was found to be highly sensitive in detecting spinal metastases even in aggressive cases. MR imaging was found to have greater reliability in detecting spinal metastases of breast cancer compared to bone scintigraphy. In conclusion, it may be important to consider the degree of malignancy of each case with spinal metastases of breast cancer in evaluating imaging diagnosis. (author).

  9. A systematic review on in vitro 3D bone metastases models: A new horizon to recapitulate the native clinical scenario?

    Science.gov (United States)

    Salamanna, Francesca; Contartese, Deyanira; Maglio, Melania; Fini, Milena

    2016-07-12

    While the skeleton is not the only organ where metastasis can occur, it is one of the preferred sites, with a significant impact in patients' quality of life. With the aim of delineating the cellular and molecular mechanisms of bone metastasis, numerous studies have been employed to identify any contributing factors that trigger cancer progression. One of the major limitations of studying cancer-bone metastasis is the multifaceted nature of the native bone environment and the lack of reliable, simple, and not expensive models that strictly mimic the biological processes occurring in vivo allowing a correct translation of results. Currently, with the growing acceptance of in vitro models as effective tools for studying cancer biology, three-dimensional (3D) models have emerged as a compromise between two-dimensional cultures of isolated cancer cells and the complexity of human cancer xenografts in immunocompromised animal hosts. This descriptive systematic literature review summarizes the current status of advanced and alternative 3D in vitro bone metastases models. We have also reviewed the strategies employed by researchers to set-up these models with special reference to recent promising developments trying to better replicate the complexity and heterogeneity of a human metastasis in situ, with an outlook at their use in medicine. All these aspects will greatly contribute to the existing knowledge on bone metastases, providing a specific link to clinical scenarios and thus making 3D in vitro bone metastasis models an attractive tool for multidisciplinary experts.

  10. Predicting the presence of extracranial metastases in patients with brain metastases upon first diagnosis of cancer

    Energy Technology Data Exchange (ETDEWEB)

    Rades, D. [University of Luebeck, Department of Radiation Oncology, Luebeck (Germany); Segedin, B. [Institute of Oncology, Department of Radiation Oncology, Ljubljana (Slovenia); Nagy, V. [Oncology Institute Ion Ciricuta, Department of Radiotherapy, Cluj-Napoca (Romania); Schild, S.E. [Mayo Clinic Scottsdale, Department of Radiation Oncology, Arizona (United States); Trang, N.T. [Bach Mai Hospital, Nuclear Medicine and Oncology Center, Hanoi (Viet Nam); Khoa, M.T. [Bach Mai Hospital, Nuclear Medicine and Oncology Center, Hanoi (Viet Nam); Hanoi Medical University, Department of Nuclear Medicine, Hanoi (Viet Nam)

    2014-04-15

    This study aimed to determine factors allowing the prediction of extracranial metastases in patients presenting with brain metastases at the first diagnosis of cancer. Data from 659 patients with brain metastases upon first diagnosis of cancer were retrospectively analyzed. The parameters age, gender, Karnofsky performance score (KPS), primary tumor type and number of brain metastases were compared between 359 patients with extracranial metastases and 300 patients without extracranial metastases. Additional analyses were performed for patients with the most unfavorable and those with the most favorable characteristics. The comparison of patients with versus without extracranial metastases revealed significant differences between the groups in terms of KPS (p < 0.001) and number of brain metastases (p < 0.001). Of the study patients, 113 had both most unfavorable characteristics, i.e. KPS ≤ 50 and ≥ 4 brain metastases. The sensitivity for identifying patients with extracranial metastases was 82 %; specificity was 51 %. A total of 50 patients had KPS ≥ 90 and only one brain metastasis. The sensitivity for identifying patients without extracranial metastases was 86 %; specificity was 58 %. The combination of KPS and the number of brain metastases can help to predict the presence or absence of extracranial metastases. (orig.) [German] Diese Studie soll zur Abschaetzung des Vorliegens extrakranieller Metastasen bei Patienten mit primaer zerebral metastasierter Tumorerkrankung beitragen. Daten von 659 Patienten mit primaer zerebral metastasierter Tumorerkrankung wurden retrospektiv analysiert. Insgesamt 359 Patienten mit extrakraniellen Metastasen wurden mit 300 Patienten ohne extrakranielle Metastasierung hinsichtlich Alter, Geschlecht, Karnofsky-Performance-Score (KPS), Art des Primaertumors und der Anzahl der Hirnmetastasen miteinander verglichen. Weitere Analysen erfolgten bei Patienten mit den unguenstigsten und bei Patienten mit den guenstigsten

  11. Limited short-term effect of palliative radiation therapy on quantitative computed tomography-derived bone mineral density in femora with metastases

    NARCIS (Netherlands)

    Eggermont, F.E.; Derikx, L.C.; Verdonschot, N.J.; Hannink, G.J.; Kaatee, R.; Tanck, E.J.; Linden, Y.M. van der

    2017-01-01

    PURPOSE: The aim of this study was to determine the effect of single fraction (SF) and multiple fraction (MF) radiation therapy (RT) on bone mineral density (BMD) in patients with cancer and bone metastases in the proximal femur. We studied this effect in the radiation field and within metastatic

  12. Could Cancer Initiate From Bone Marrow Progenitors?

    OpenAIRE

    Ben Nasr, Hmed; Hammami, Serria Turky; Zeghal, Khaled

    2013-01-01

    Background Defining cancer stem cells and their origins is of much controversy,and constitutes a challenged knockout for cell targeting- anticancer drugs. Herein,we put forward a hypothetic model for cancer stem cells initiation from bone marrow stem cells. These later, will differentiate into an ancestral progenitor that activates a memorial program - the black box cassette- that is responsible of abnormal neo-organogenesis in the form of tumors and metastases. To approve this model, we assu...

  13. Radiotherapy for bone metastases; Perkutane Strahlentherapie von Knochenmetastasen

    Energy Technology Data Exchange (ETDEWEB)

    Schueller, H.; Wisser, L.; Pauleit, D. [Bonn Univ. (Germany). Radiologische Klinik

    1997-09-01

    Bone metastases causing pain syndromes and imminent pathologic fractures are among the main reasons for radiotherapy in patients suffering from malignant tumors. The indication is much influenced by the radiologic findings. Surgical methods are to be chosen in the first place in cases of pathologic fractures or patients with a high risk of such fractures. Different authors recommend various therapeutic regimens. Effective pain control can be achieved with one single dose of radiation. Doses of 6 to 40 Gy applied in one to 19 days are also efficient. Side effects, especially nausea and vomiting occur in 25% of cases; this number rises to 50% in cases of half body irradiation. Visible changes of bone mineral density may be noticed about 6 weeks after termination of radiotherapy. About 70% of osteolytic metastases show progressive sclerosis whereas osteosclerotic lesions may show both increase or decline of bone mass. In spite many years of experience the optimal strategy for radiation therapy of bone metastasis has not been defined; further studies are needed. (orig.) [Deutsch] Metastasenbedingte Schmerzsyndrome und die Verhuetung von pathologischen Frakturen sind die haeufigsten Indikationen zur perkutanen Strahlentherapie bei Tumorpatienten mit Knochenmetastasen. Die Therapieindikation und Zuordnung zu einer Risikogruppe wird vom Roentgenbild mitbeeinflusst. Bei einem hohen Risiko einer pathologischen Fraktur und bei der Behandlung, pathologischer Frakturen sind zunaechst die Moeglichkeiten einer operativen Behandlung auszuschoepfen. Die Therapiemodalitaeten der perkutanen Strahlentherapie variieren bei den verschiedenen Autoren betraechtlich. Eine effektive Schmerzlinderung ist bereits mit einer einmaligen Bestrahlung zu erzielen. Strahlendosen von 6-40 Gy, appliziert in einem Zeitraum von einem bis zu 19 Tagen, erweisen sich als wirksam. Nebenwirkungen - vor allem Uebelkeit und Erbrechen - beeintraechtigen etwa ein Viertel der Patienten. Bei einer

  14. Cancer Cell Colonisation in the Bone Microenvironment

    Directory of Open Access Journals (Sweden)

    Casina Kan

    2016-10-01

    Full Text Available Bone metastases are a common complication of epithelial cancers, of which breast, prostate and lung carcinomas are the most common. The establishment of cancer cells to distant sites such as the bone microenvironment requires multiple steps. Tumour cells can acquire properties to allow epithelial-to-mesenchymal transition, extravasation and migration. Within the bone metastatic niche, disseminated tumour cells may enter a dormancy stage or proliferate to adapt and survive, interacting with bone cells such as hematopoietic stem cells, osteoblasts and osteoclasts. Cross-talk with the bone may alter tumour cell properties and, conversely, tumour cells may also acquire characteristics of the surrounding microenvironment, in a process known as osteomimicry. Alternatively, these cells may also express osteomimetic genes that allow cell survival or favour seeding to the bone marrow. The seeding of tumour cells in the bone disrupts bone-forming and bone-resorbing activities, which can lead to macrometastasis in bone. At present, bone macrometastases are incurable with only palliative treatment available. A better understanding of how these processes influence the early onset of bone metastasis may give insight into potential therapies. This review will focus on the early steps of bone colonisation, once disseminated tumour cells enter the bone marrow.

  15. Percutaneous Thermal Ablation of Breast Cancer Metastases in Oligometastatic Patients

    Energy Technology Data Exchange (ETDEWEB)

    Barral, M., E-mail: matthias-barral@yahoo.fr [Institut Gustave Roussy, Interventional Radiology Department (France); Auperin, A., E-mail: anne.auperin@gustaveroussy.fr [Institut Gustave Roussy, Biostatistics and Epidemiology Unit (France); Hakime, A., E-mail: thakime@yahoo.com; Cartier, V., E-mail: victoirecartier@hotmail.com; Tacher, V., E-mail: vaniatacher@gmail.com [Institut Gustave Roussy, Interventional Radiology Department (France); Otmezguine, Yves, E-mail: yotmezguine@ccps.com [Centre Clinique de la Porte de Saint-Cloud, Radiotherapy (France); Tselikas, L., E-mail: lambros.tselikas@gmail.com; Baere, T. de, E-mail: thierry.debaere@gustaveroussy.fr; Deschamps, F., E-mail: frederic.deschamps@gustaveroussy.fr [Institut Gustave Roussy, Interventional Radiology Department (France)

    2016-06-15

    ObjectiveTo evaluate prognostic factors associated with local control and disease-free-survival (DFS) of oligometastatic breast cancer patients treated by percutaneous thermal ablation (PTA).Materials and MethodsSeventy-nine consecutive patients (54.5 ± 11.2 years old) with 114 breast cancer metastases (28.9 ± 16.1 mm in diameter), involving the lungs, the liver, and/or the bone, were treated using PTA with a curative intent. The goal was to achieve a complete remission in association with systemic chemotherapy and hormonal therapy. We retrospectively evaluated the prognostic factors associated with 1- and 2-year local control and the 1- and 2-year DFS rates.ResultsThe 1- and 2-year local control rates were 83.0 and 76.1 %, respectively. Tumor burden was associated with a poorer outcome for local control after PTA (HR 1.027 by additional millimeter, p = 0.026; >4 cm HR 3.90). The 1- and 2-year DFS rates were 54.2 and 30.4 %, respectively. In multivariate analysis, triple-negative histological subtype and increased size of treated metastases were associated with a poorer DFS (HR 2.22; 95 % CI [1.13–4.36]; p = 0.02 and HR 2.43; 95 % CI [1.22–4.82]; p = 0.011, respectively).ConclusionPTA is effective for local control of breast cancer oligometastases. Tumor burden >4 cm and triple-negative histological subtype are associated with a poorer outcome.

  16. A radiobiological model of metastatic burden reduction for molecular radiotherapy: application to patients with bone metastases

    Science.gov (United States)

    Denis-Bacelar, Ana M.; Chittenden, Sarah J.; Murray, Iain; Divoli, Antigoni; McCready, V. Ralph; Dearnaley, David P.; O'Sullivan, Joe M.; Johnson, Bernadette; Flux, Glenn D.

    2017-04-01

    Skeletal tumour burden is a biomarker of prognosis and survival in cancer patients. This study proposes a novel method based on the linear quadratic model to predict the reduction in metastatic tumour burden as a function of the absorbed doses delivered from molecular radiotherapy treatments. The range of absorbed doses necessary to eradicate all the bone lesions and to reduce the metastatic burden was investigated in a cohort of 22 patients with bone metastases from castration-resistant prostate cancer. A metastatic burden reduction curve was generated for each patient, which predicts the reduction in metastatic burden as a function of the patient mean absorbed dose, defined as the mean of all the lesion absorbed doses in any given patient. In the patient cohort studied, the median of the patient mean absorbed dose predicted to reduce the metastatic burden by 50% was 89 Gy (interquartile range: 83-105 Gy), whilst a median of 183 Gy (interquartile range: 107-247 Gy) was found necessary to eradicate all metastases in a given patient. The absorbed dose required to eradicate all the lesions was strongly correlated with the variability of the absorbed doses delivered to multiple lesions in a given patient (r  =  0.98, P  clinical practice for patient selection and to indicate the required administered activity to achieve a predicted patient mean absorbed dose and reduction in metastatic tumour burden.

  17. Osteoprotegerin in Bone Metastases: Mathematical Solution to the Puzzle

    Science.gov (United States)

    Ryser, Marc D.; Qu, Yiding; Komarova, Svetlana V.

    2012-01-01

    Bone is a common site for cancer metastasis. To create space for their growth, cancer cells stimulate bone resorbing osteoclasts. Cytokine RANKL is a key osteoclast activator, while osteoprotegerin (OPG) is a RANKL decoy receptor and an inhibitor of osteoclastogenesis. Consistently, systemic application of OPG decreases metastatic tumor burden in bone. However, OPG produced locally by cancer cells was shown to enhance osteolysis and tumor growth. We propose that OPG produced by cancer cells causes a local reduction in RANKL levels, inducing a steeper RANKL gradient away from the tumor and towards the bone tissue, resulting in faster resorption and tumor expansion. We tested this hypothesis using a mathematical model of nonlinear partial differential equations describing the spatial dynamics of OPG, RANKL, PTHrP, osteoclasts, tumor and bone mass. We demonstrate that at lower expression rates, tumor-derived OPG enhances the chemotactic RANKL gradient and osteolysis, whereas at higher expression rates OPG broadly inhibits RANKL and decreases osteolysis and tumor burden. Moreover, tumor expression of a soluble mediator inducing RANKL in the host tissue, such as PTHrP, is important for correct orientation of the RANKL gradient. A meta-analysis of OPG, RANKL and PTHrP expression in normal prostate, carcinoma and metastatic tissues demonstrated an increase in expression of OPG, but not RANKL, in metastatic prostate cancer, and positive correlation between OPG and PTHrP in metastatic prostate cancer. The proposed mechanism highlights the importance of the spatial distribution of receptors, decoys and ligands, and can be applied to other systems involving regulation of spatially anisotropic processes. PMID:23093918

  18. Osteoprotegerin in bone metastases: mathematical solution to the puzzle.

    Directory of Open Access Journals (Sweden)

    Marc D Ryser

    Full Text Available Bone is a common site for cancer metastasis. To create space for their growth, cancer cells stimulate bone resorbing osteoclasts. Cytokine RANKL is a key osteoclast activator, while osteoprotegerin (OPG is a RANKL decoy receptor and an inhibitor of osteoclastogenesis. Consistently, systemic application of OPG decreases metastatic tumor burden in bone. However, OPG produced locally by cancer cells was shown to enhance osteolysis and tumor growth. We propose that OPG produced by cancer cells causes a local reduction in RANKL levels, inducing a steeper RANKL gradient away from the tumor and towards the bone tissue, resulting in faster resorption and tumor expansion. We tested this hypothesis using a mathematical model of nonlinear partial differential equations describing the spatial dynamics of OPG, RANKL, PTHrP, osteoclasts, tumor and bone mass. We demonstrate that at lower expression rates, tumor-derived OPG enhances the chemotactic RANKL gradient and osteolysis, whereas at higher expression rates OPG broadly inhibits RANKL and decreases osteolysis and tumor burden. Moreover, tumor expression of a soluble mediator inducing RANKL in the host tissue, such as PTHrP, is important for correct orientation of the RANKL gradient. A meta-analysis of OPG, RANKL and PTHrP expression in normal prostate, carcinoma and metastatic tissues demonstrated an increase in expression of OPG, but not RANKL, in metastatic prostate cancer, and positive correlation between OPG and PTHrP in metastatic prostate cancer. The proposed mechanism highlights the importance of the spatial distribution of receptors, decoys and ligands, and can be applied to other systems involving regulation of spatially anisotropic processes.

  19. miR-20b is up-regulated in brain metastases from primary breast cancers

    Science.gov (United States)

    Ahmad, Aamir; Ginnebaugh, Kevin R.; Sethi, Seema; Chen, Wei; Ali, Rouba; Mittal, Sandeep; Sarkar, Fazlul H.

    2015-01-01

    Brain metastases are frequent in patients with advanced breast cancer and are associated with poor prognosis. However, unique molecular biomarkers have not yet been established. We hypothesized that microRNA-20b (miR-20b) plays a role in breast cancer brain metastasis. Our study cohort comprised of eleven breast cancer patients with brain metastasis and nine control patients (age, stage, and follow-up matched) with breast cancer without brain metastasis. Cases were reviewed microscopically to select tumor blocks with >50% tumor cells, RNA was extracted from formalin-fixed paraffin-embedded (FFPE) tumor tissue blocks and expression of miR-20b analyzed using qRT-PCR. We further tested the effect of miR-20b overexpression on colony formation and invasion in vitro using MCF-7 and MDA-MB-231 cells. In the patient-derived samples, miR-20b expression was significantly higher in brain metastases of breast cancer patients, compared to primary breast tumors as well as the patients without brain metastasis. miR-20b also significantly induced the colony formation and invasiveness of breast cancer cells. Further, miR-20b levels were observed to be high in brain-metastasizing cells, compared to bone-metastasizing cells. Together, our findings suggest a novel role of miR-20b in breast cancer brain metastasis that warrants further investigation for its potential to be developed as prognostic and/or therapeutic target. PMID:25893380

  20. Non-invasive assessment of inter-and intrapatient variability of integrin expression in metastasized prostate cancer by PET.

    Science.gov (United States)

    Beer, Ambros J; Schwarzenböck, Sarah M; Zantl, Niko; Souvatzoglou, Michael; Maurer, Tobias; Watzlowik, Petra; Kessler, Horst; Wester, Hans-Jürgen; Schwaiger, Markus; Krause, Bernd Joachim

    2016-05-10

    Due to the high expression of the integrin αvβ3 not only on endothelial cells, but also on mature osteoclasts and prostate cancer cells, imaging of osseous metastases with αvβ3-targeted tracers seems promising. However, little is known about the patterns of αvβ3-expression in metastasized prostate cancer lesions in-vivo. Thus we evaluated the uptake of the αvβ3-specific PET tracer [18F]Galacto-RGD for assessment of bone metastases in prostate cancer patients. [18F]Galacto-RGD PET identified 58/74 bone-lesions (detection rate of 78.4%) and lymph node metastases in 2/5 patients. The SUVmean was 2.12+/-0.94 (range 0.70-4.38; tumor/blood 1.36+/-0.53; tumor/muscle 2.82+/-1.31) in bone-lesions and 2.21+/-1.18 (range 0.75-3.56) in lymph node metastases. Good visualization and detection of bone metastases was feasible due to a low background activity of the surrounding normal bone tissue. 12 patients with known metastasized prostate cancer according to conventional staging (including bone-scintigraphy and contrast-enhanced CT; median PSA 68.63 ng/ml, range 3.72-1935) were examined with PET after i.v.-injection of [18F]Galacto-RGD. Two blinded nuclear-medicine physicians evaluated the PET-scans in consensus concerning lesion detectability. Volumes-of-interest were drawn in the PET-scans over all metastases defined by conventional staging (maximum of 11 lesions/patient), over the left ventricle, liver and muscle and standardized-uptake-values (SUVs) were calculated. Our data show generally elevated uptake of [18F]Galacto-RGD in bone metastases from prostate cancer with a marked inter- and intrapatient variability. While [18F]Galacto-RGD PET is inferior to bone scintigraphy for detection of osseous metastases, it might be valuable in patient screening and monitoring of αvβ3-targeted therapies due to the high variability of αvβ3-expression.

  1. The Use of Corticosteroids as Adjuvant Therapy for Painful Bone Metastases: A Large Cross-Sectional Survey of Palliative Care Providers.

    Science.gov (United States)

    White, Patrick; Arnold, Robert; Bull, Janet; Cicero, Brandon

    2018-01-01

    Bone metastases are a common complication in patients with advanced cancer but little is known regarding current practice patterns of palliative care providers when prescribing corticosteroids as adjuvant therapy for painful bone metastases. To identify current practice patterns among palliative care providers when prescribing corticosteroids for the treatment of painful bone metastases. A cross-sectional, online survey of the membership of the American Academy of Hospice and Palliative Medicine. Providers were asked to report how frequently they prescribed corticosteroids as adjuvant therapy in patients with painful bone metastases, and to specify the corticosteroid, dosage, treatment duration, and the gastroprotective strategy most frequently utilized. Seven hundred sixty-five participants responded to the survey and 600 (78%) of respondents completed the survey. Ninety-eight percent of respondents completing the survey reported having prescribed corticosteroids as adjuvant pain therapy, and 66% ordered corticosteroids for the majority of their patients with painful bone metastases. Dexamethasone was the most widely prescribed corticosteroid. Eight milligrams divided twice daily was the most common dosage selected and once started, it was usually continued indefinitely. Corticosteroids are commonly prescribed as adjuvant therapy in the treatment of painful bone metastases in patients with limited life expectancy. Dexamethasone is the most commonly selected corticosteroid by American palliative care providers with variation existing among providers regarding dosing schedule, treatment duration, and gastroprotective strategies. Clinical trials comparing a total daily dose of four versus eight milligrams of dexamethasone would be clinically useful to inform evidence-based practice.

  2. TU-A-12A-08: Computing Longitudinal Material Changes in Bone Metastases Using Dual Energy Computed Tomography

    Energy Technology Data Exchange (ETDEWEB)

    Schmidtlein, CR; Hwang, S; Veeraraghavan, H; Fehr, D; Humm, J; Deasy, J [Memorial Sloan Kettering Cancer Center, New York, NY (United States)

    2014-06-15

    Purpose: This study demonstrates a methodology for tracking changes in metastatic bone disease using trajectories in material basis space in serial dual energy computed tomography (DECT) studies. Methods: This study includes patients with bone metastases from breast cancer that had clinical surveillance CT scans using a General Electric CT750HD in dual energy mode. A radiologist defined regions-of-interested (ROI) for bone metastasis, normal bone, and marrow across the serial DECT scans. Our approach employs a Radon transform to forward-projection the basis images, namely, water and iodine, into sinogram space. This data is then repartitioned into fat/bone and effective density/Z image pairs using assumed energy spectrums for the x-ray energies. This approach both helps remove negative material densities and avoids adding spectrum-hardening artifacts. These new basis data sets were then reconstructed via filtered back-projection to create new material basis pair images. The trajectories of these pairs were then plotted in the new basis space providing a means to both visualize and quantitatively measure changes in the material properties of the tumors. Results: ROI containing radiologist defined metastatic bone disease showed well-defined trajectories in both fat/bone and effective density/Z space. ROI that contained radiologist defined normal bone and marrow did not exhibit any discernible trajectories and were stable from scan to scan. Conclusions: The preliminary results show that changes in material composition and effective density/Z image pairs were seen primarily in metastasis and not in normal tissue. This study indicates that by using routine clinical DECT it may be possible to monitor therapy response of bone metastases because healing or worsening bone metastases change material composition of bone. Additional studies are needed to further validate these results and to test for their correlation with outcome.

  3. Race does not predict the development of metastases in men with nonmetastatic castration-resistant prostate cancer.

    Science.gov (United States)

    Whitney, Colette A; Howard, Lauren E; Amling, Christopher L; Aronson, William J; Cooperberg, Matthew R; Kane, Christopher J; Terris, Martha K; Freedland, Stephen J

    2016-12-15

    Although race is associated with prostate cancer progression in early stage disease, once men have advanced disease, it is unclear whether race continues to predict a poor outcome. The authors hypothesized that, in an equal-access setting among patients with castration-resistant prostate cancer (CRPC) and no known metastases (M0/Mx), black men would receive imaging tests at similar rates as nonblack men (ie, there would be an equal opportunity to detect metastases) but would have a higher risk of metastatic disease. In total, 837 men who were diagnosed with M0/Mx CRPC during 2000 through 2014 from 5 Veterans Affairs hospitals in the SEARCH (Shared Equal Access Regional Cancer Hospital) database were analyzed. Data on all imaging tests after CRPC diagnosis were collected, including date, type, and outcome. Multivariable Cox models were used to test associations between race and the time to first metastasis, first bone metastasis, first bone scan, second bone scan among men who had a negative first bone scan, and overall survival. Black men (n = 306) were equally as likely as nonblack men (n = 531) to receive a first and second bone scan after a diagnosis of CRPC. There were no significant differences in the risk of developing any metastases, bone metastases, time to bone scans, or overall survival between black men and nonblack men (all P > .2). The lack of racial differences in the development of metastases and scanning practices observed in this study suggests that, once men have a diagnosis of M0/Mx CRPC, race may not be a prognostic factor. Efforts to understand prostate cancer racial disparities may derive greater benefit by focusing on the risk of developing prostate cancer and on the outcomes of men who have early stage disease. Cancer 2016;122:3848-3855. © 2016 American Cancer Society. © 2016 American Cancer Society.

  4. Photodynamic therapy for cutaneous metastases of breast cancer

    Directory of Open Access Journals (Sweden)

    E. V. Goranskaya

    2011-01-01

    Full Text Available Breast cancer is the most common cancer and the leading cause of cancer death in w omen. Cutaneous metastases are observed in 20 % pa- tients with breast cancer. 36 breast cancer patients with cutaneous metastases were treated with photodynamic therapy in the de partment of laser and photodynamic therapy MRRC. Complete regression was obtained in 33.9 %, partial — in 39 % of cases, the stabilization achieved in 25.4 %, progression noted in 1.7 %. The objective response was obtained in 72.9 % of cases, treatment effect — in 97.4 %. Photodynamic therapy has good treatment results of cutaneous metastases of breast cancer with a small number of side effects.

  5. Risk factors for disease progression in HER2-positive breast cancer patients based on the location of metastases

    Directory of Open Access Journals (Sweden)

    Joanna Huszno

    2015-09-01

    Full Text Available Introduction : Trastuzumab therapy significantly improves progression-free and overall survival in HER2-positive [HER2(+] breast cancer (BC patients. However, in most patients with HER2(+ metastatic BC, the disease progress occurred. The aim of this study was to evaluate the clinicopathological risk factors for progression in HER2-positive breast cancer patients during trastuzumab therapy. Material and methods : The analysis included medical records of HER2(+ metastatic BC patients treated with trastuzumab between 2006 and 2013. Results : The most common site of progression during trastuzumab therapy were lungs 25 (39%, central nervous system (CNS 8 (13%, skin 9 (14%, locoregional lymph nodes 19 (30%, liver 18 (28% and bone 17 (27%. Patients with lung metastases significantly more often had a history of cancer in the family than women with other metastasis sites (24% vs. 2.6%, p = 0.048. Metastases to lungs occurred also more often during therapy containing trastuzumab with chemotherapy than trastuzumab alone 17/8 (58% vs. 41%, p = 0.043. Central nervous system metastases were observed insignificantly more frequently in postmenopausal women than premenopausal patients 8/0 (22% vs. 0%, p = 0.093. There was reported a tendency to liver metastases in ER-negative tumors 13/20 (72% vs. 44%, p = 0.053. Bone metastases were associated with the positive steroid receptor status (p = 0.019 and second neoplasm in history (p = 0.06. Conclusions : Risk factors for disease progression were the menopausal status (CNS metastases, steroid receptor status (liver, lymph nodes and bone metastases, history of cancer in the family (lung metastases and history of cigarette smoking (liver metastases.

  6. Leptomeningeal disease following stereotactic radiosurgery for brain metastases from breast cancer.

    Science.gov (United States)

    Trifiletti, Daniel M; Romano, Kara D; Xu, Zhiyuan; Reardon, Kelli A; Sheehan, Jason

    2015-09-01

    Leptomeningeal disease (LMD) is a highly aggressive and usually rapidly fatal condition. The purpose of this study is to identify clinical factors that can serve to predict for LMD at the time of stereotactic radiosurgery (SRS) for brain metastases from breast carcinoma. We conducted a retrospective review of patients with brain metastases from breast cancer treated with SRS from 1995 to 2014 at our institution. Clinical, radiographic, and dosimetric data were collected. LMD was diagnosed by cerebrospinal fluid (CSF) cytology or MRI demonstrating CSF seeding. Comparative statistical analyses were conducted using Cox proportional hazards regression, binary logistic regression, and/or log-rank test. 126 patients met inclusion criteria. Eighteen patients (14 %) developed LMD following SRS. From the time of SRS, the actuarial rate of LMD at 12 months from diagnosis of brain metastasis was 9 % (11 patients). Active disease in the chest at the time of SRS was associated with development of LMD (p = 0.038). Factors including receptor status, tumor size, number of intra-axial tumors, cystic tumor morphology, prior WBRT, active bone metastases, and active liver metastases were not significantly associated with the development of LMD. In patients with brain metastasis from breast cancer that undergo SRS, there is a relatively low rate of LMD. We found that while tumor hormonal status, bone metastases, and hepatic metastases were not associated with the development of LMD, active lung metastases at SRS was associated with LMD. Further research may help to delineate a causative relationship between metastatic lung disease and LMD.

  7. Liver metastases

    Science.gov (United States)

    ... CT scan of the abdomen Liver function tests Liver biopsy MRI of the abdomen PET scan Ultrasound of ... Lung cancer - liver metastases; Melanoma - liver metastases Images Liver biopsy Hepatocellular cancer, CT scan Liver metastases, CT scan ...

  8. Sclerosing epithelioid fibrosarcoma of the thigh: report of two cases with synchronous bone metastases.

    Science.gov (United States)

    Righi, A; Gambarotti, M; Manfrini, M; Benini, S; Gamberi, G; Cocchi, S; Casadei, R; Picci, P; Vanel, D; Dei Tos, A P

    2015-09-01

    We report two cases of sclerosing epithelioid fibrosarcoma occurring in the deep soft tissue of the thigh, confirmed by molecular analysis and associated with bone metastases in the lumbar vertebrae and the iliac wing at the time of diagnosis. Synchronous bone metastases of sclerosing epithelioid fibrosarcoma are extremely difficult to diagnose because clinical and radiological features are not specific. In addition, the range of differential diagnoses is very wide, including metastatic carcinoma and osteosarcoma. At present, all but three published cases of sclerosing epithelioid fibrosarcoma with bone metastases showed bone metastases during follow-up. We confirm in our two cases that the distinct pattern of immunohistochemical staining for MUC4, associated with the absence of staining for both SATB2, a marker of osteoblastic differentiation, and pan-cytokeratin, allows differentiating between sclerosing epithelioid fibrosarcoma and metastatic carcinoma or osteosarcoma.

  9. Reflections on the therapeutic use of {sup 223}RaCl{sub 2} for bone metastases resulting from prostate cancer resistant to castration; Reflexiones sobre el uso terapeutico de {sup 223}RaCl{sub 2} para metastasis osea derivada de cancer de prostata resistente a la castracion

    Energy Technology Data Exchange (ETDEWEB)

    Astudillo V, A. J.; Paredes G, L., E-mail: armando.astudillo@inin.gob.mx [ININ, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico)

    2015-10-15

    In January 2014 the Comision Federal para la Proteccion contra Riesgos Sanitarios of the Ministry of Health in Mexico, authorize the use of {sup 223}RaCl{sub 2} as the first radiopharmaceutical emitter α for therapeutic purposes in cases of bone metastases resulting from prostate cancer resistant to castration. The paper analyzes the main variables that affect the metrological traceability using activity meters to evaluate the gamma activity of {sup 223}RaCl{sub 2} in hospitals, because it has a chain of complex decay with alpha, beta and gamma emitters, so was important to verify if a gamma activity measurement for a multiple emitter is reliable to determine the total alpha absorbed dose to bone in a patient. (Author)

  10. Clinical features and prognostic factors in patients with bone metastases from hepatocellular carcinoma after liver transplantation

    Directory of Open Access Journals (Sweden)

    He Jian

    2011-11-01

    Full Text Available Abstract Background Little is known about the clinical features and prognostic factors of bone metastases of hepatocellular carcinoma (HCC following liver transplantation (LT. Methods All adult patients undergoing LT from 2001 to 2010 were reviewed. Patients with HCC bone metastases after LT received external beam radiotherapy(EBRT during this period. Demographic variables, laboratory values, and tumor characteristics were determined before LT and EBRT. Total radiation dose ranged from 8 to 60 Gy(median dose 40.0 Gy. Results The trunk was the most common site of bone metastases with finding of expansile soft-tissue masses in 23.3% of patients. Overall pain relief from EBRT occurred in 96.7% (29/30. No consistent dose-response relationship was found for palliation of with doses between 30 and 56 Gy (P = 0.670. The median survivals from the time of bone metastases was 8.6 months. On univariate and multivariate analyses, better survival was significantly associated with a better Karnofsky performance status (KPS and well-controlled intrahepatic tumor, but not with lower alpha-fetoprotein levels. The median time from LT to bone metastases was 7.1 months. Patients exceeding the Shanghai criteria presented with bone metastases earlier than those within the Fudan criteria. Patients with soft-tissue extension always had later bone metastases. The majority of deaths were caused by liver failure due to hepatic decompensation or tumor progression. Conclusion The prognostic factors of bone metastases of HCC following LT are KPS and well-controlled intrahepatic. Even though survival is shorter for these patients, EBRT provides effective palliation of pain.

  11. Establishment of an experimental human lung adenocarcinoma cell line SPC-A-1BM with high bone metastases potency by {sup 99m}Tc-MDP bone scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Yang Shunfang [Department of Nuclear Medicine, Shanghai Chest Hospital of Shanghai Jiaotong University, Shanghai 200030 (China)], E-mail: yzyg@sh163.net; Dong Qianggang [Laboratory of Mol-diagnosis, Shanghai Cancer Institute of Shanghai Jiaotong University, Shanghai 200032 (China); Yao Ming [Laboratory of Pathology, Shanghai Cancer Institute of Shanghai Jiaotong University, Shanghai 200032 (China); Shi Meiping [Department of Pathology, Shanghai Chest Hospital of Shanghai Jiaotong University, Shanghai 200030 (China); Ye Jianding [Department of Radiology, Shanghai Chest Hospital of Shanghai Jiaotong University, Shanghai 200030 (China); Zhao Langxiang [Department of Pathology, Shanghai Chest Hospital of Shanghai Jiaotong University, Shanghai 200030 (China); Su Jianzhong; Gu Weiyong [Shanghai Thoracic Tumor Institute, Shanghai Chest Hospital of Shanghai Jiaotong University, Shanghai 200030 (China); Xie Wenhui [Department of Nuclear Medicine, Shanghai Chest Hospital of Shanghai Jiaotong University, Shanghai 200030 (China); Wang Kankan; Du Yanzhi [State Key Laboratory of Medical Genomics, Ruijin Hospital of Shanghai Jiaotong University, Shanghai 200025 (China); Li Yao [State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai 200433 (China); Huang Yan [State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai 200433 (China)], E-mail: huangyan@fudan.edu.cn

    2009-04-15

    Background: Bone metastasis is one of the most common clinical phenomena of late stage lung cancer. A major impediment to understanding the pathogenesis of bone metastasis has been the lack of an appropriate animal and cell model. This study aims to establish human lung adenocarcinoma cell line with highly bone metastases potency with {sup 99m}Tc-MDP bone scintigraphy. Methods: The human lung adenocarcinoma cancer cells SPC-A-1 were injected into the left cardiac ventricle of NIH-Beige-Nude-XID (NIH-BNX) immunodeficient mice. The metastatic lesions of tumor-bearing mice were imaged with {sup 99m}Tc-MDP bone scintigraphy on a Siemens multi-single photon emission computed tomography. Pinhole images were acquired on a GZ-B conventional gamma camera with a self-designed pinhole collimator. The mice with bone metastasis were sacrificed under deep anesthesia, and the lesions were resected. Bone metastatic cancer cells in the resected lesions were subjected for culture and then reinoculated into the NIH-BNX mice through left cardiac ventricle. The process was repeated for eight cycles to obtain a novel cell subline SPC-A-1BM. Real-time polymerase chain reaction (PCR) was used to compare the gene expression differences in the parental and SPC-A-1BM cells. Results: The bone metastasis sites were successfully revealed by bone scintigraphy. The established bone metastasis cell line SPC-A-1BM had a high potential to metastasize in bone, including mandible, humerus, thoracic vertebra, lumbar, femur, patella, ilium and cartilage rib. The expression level of vascular endothelial growth factor gene family, Bcl-2 and cell adhesion-related genes ECM1, ESM1, AF1Q, SERPINE2 and FN1 were examined. Gene expression difference was found between parental and bone-seeking metastasis cell SPC-A-1BM, which indicates SPC-A-1BM has metastatic capacity vs. its parental cells. Conclusion: SPC-A-1BM is a bone-seeking metastasis human lung adenocarcinoma cell line. Bone scintigraphy may be used as

  12. Pain and quality of life following palliative radiotherapy of bone metastases; Der Einfluss palliativer Strahlentherapie auf Schmerz und Lebensqualitaet bei Patienten mit Knochenmetastasen

    Energy Technology Data Exchange (ETDEWEB)

    Sauer, N.; Wild, B.; Henningsen, P.; Jakobsen, T. [Klinik fuer Psychosomatische und Allgemeine Klinische Medizin, Univ. Heidelberg (Germany); Leising, D. [Inst. fuer Psychologie, Univ. Wuerzburg (Germany); Treiber, M. [Radiologische Universitaetsklinik, Heidelberg (Germany)

    2006-09-15

    Pain and quality of life following palliative radiotherapy of bone metastases Background and purpose: palliative irradiation is used to provide pain relief and to increase quality of life. Most studies exclude patients with advanced cancer disease and, therefore, a positive selection results. This prospective clinical study investigates the effect of palliative radiotherapy on pain and quality of life of patients with painful bone metastases. Patients and methods: 263 patients with bone metastases due to advanced cancer were observed with respect to pain and quality of life during a 2-month course of radiotherapy. Missing data were substituted by the LOCF method (last observation carried forward) to prevent a biased reduction of data. Results: radiotherapy resulted in pain relief. In the complete group, pain medication was not increased. Quality of life was not affected positively. Side effects of radiotherapy increased remarkably. Conclusion: Radiotherapy leads to pain relief. However, risks and benefits must be considered critically due to side effects. (orig.)

  13. Optimal bone health management strategies in patients with prostate cancer

    Directory of Open Access Journals (Sweden)

    Gagan Prakash

    2013-01-01

    Full Text Available Bone health is affected in patients with prostate cancer, both by the disease and its treatment. Metastases to bone leads to pain, fractures, and spinal cord compression; bone loss due to androgen deprivation therapy (ADT leads to osteoporosis and its complications. Both these scenarios are a major cause of morbidity and adversely affect the quality of life of these patients. Maintaining an optimum bone health throughout the natural course of prostate cancer is an important aspect in the management of this disease. An understanding of the complex interplay between osteoclasts, osteoblasts, receptor activator of nuclear factor κB (RANK, and various other tyrosine kinases involved in the pathophysiology of bone metastases is essential. Zoledronic acid (ZA, an intravenously administered bisphosphonate, and Denosumab, a subcutaneously administered inhibitor of nuclear factor B ligand (RANKL, have already been approved by Food and Drug Administration (FDA for their use in treatment of bone metastases. This article discusses the pathophysiology of bone metastases and bone loss due to ADT in prostate cancer, role of biomarkers, newer modalities of imaging, World Health Organization (WHO/FRAX nomogram in evaluation of these patients, utility of currently available drugs and evidence supporting their use, and newer therapeutic agents like alpha-emitting Radium-223, endothelin-A receptor antagonists (Atrasentan and Zibotentan and the proto-oncogene tyrosine-protein kinase (SRC inhibitor, Dasatinib.

  14. Molecular Concordance Between Primary Breast Cancer and Matched Metastases

    DEFF Research Database (Denmark)

    Krøigård, Anne Bruun; Larsen, Martin Jakob; Thomassen, Mads

    2016-01-01

    . The purpose of this review is to illuminate the extent of cancer genome evolution through disease progression and the degree of molecular concordance between primary breast cancers and matched metastases. We present an overview of the most prominent studies investigating the expression of endocrine receptors......Clinical management of breast cancer is increasingly personalized and based on molecular profiling. Often, primary tumors are used as proxies for systemic disease at the time of recurrence. However, recent studies have revealed substantial discordances between primary tumors and metastases, both......, transcriptomics, and genome aberrations in primary tumors and metastases. In conclusion, biopsy of metastatic lesions at recurrence of breast cancer is encouraged to provide optimal treatment of the disease. Furthermore, molecular profiling of metastatic tissue provides invaluable mechanistic insight...

  15. Concurrent dendritic cell vaccine and strontium-89 radiation therapy in the management of multiple bone metastases.

    Science.gov (United States)

    Liu, J; Li, J; Fan, Y; Chang, K; Yang, X; Zhu, W; Wu, X; Pang, Yan

    2015-06-01

    In addition to its direct cytotoxic effects, radiation therapy renders tumor cells more susceptible to T cell-mediated cytotoxicity by modulating cell surface molecules involved in antigen presentation. The purpose of the present study was to determine the benefit of combined 89Sr radiation and dendritic cell (DC) vaccine therapy in bone metastasis patients. Patients were treated with intravenous 89Sr at a dose of 40 μCi/kg of body weight on the first day after the peripheral blood mononuclear cell collection. Seven days later, patients received DCs once a week for 6 weeks. The first three vaccines were administered by intravenous infusion, and the last three vaccines were administered by 24-point intradermal injection. Clinical response was evaluated by the number of bone metastatic foci demonstrated on bone scintigraphy; cell-mediated cytotoxicity response was evaluated by delayed-type hypersensitivity (DTH) reaction. All treatment-related toxicities including vaccine-induced fever and 89Sr-associated hematological toxicity were carefully monitored. Twenty-six patients with histologically diagnosed with primary cancers and multiple bone metastases demonstrated on bone scintigraphy were studied. The overall survival rate was 58.3%. The total positive DTH rate was 50%. The efficiency rate for pain relief was 60% (6/10), for quantity of life was 80%, and for clinic responses was 90%. Out of 10 cases, the Grade 1 or 2 of hematological depression in 4, erythema in 1, and fever in 7 were observed. The study has important implications for that combined 89Sr radiation, and DC vaccine therapy can benefit cancer patients with bone metastasis.

  16. LIGHT Elevation Enhances Immune Eradication of Colon Cancer Metastases.

    Science.gov (United States)

    Qiao, Guilin; Qin, Jianzhong; Kunda, Nicholas; Calata, Jed F; Mahmud, Dolores L; Gann, Peter; Fu, Yang-Xin; Rosenberg, Steven A; Prabhakar, Bellur S; Maker, Ajay V

    2017-04-15

    The majority of patients with colon cancer will develop advanced disease, with the liver being the most common site of metastatic disease. Patients with increased numbers of tumor-infiltrating lymphocytes in primary colon tumors and liver metastases have improved outcomes. However, the molecular factors that could empower antitumor immune responses in this setting remain to be elucidated. We reported that the immunostimulatory cytokine LIGHT (TNFSF14) in the microenvironment of colon cancer metastases associates with improved patient survival, and here we demonstrate in an immunocompetent murine model that colon tumors expressing LIGHT stimulate lymphocyte proliferation and tumor cell-specific antitumor immune responses. In this model, increasing LIGHT expression in the microenvironment of either primary tumors or liver metastases triggered regression of established tumors and slowed the growth of liver metastases, driven by cytotoxic T-lymphocyte-mediated antitumor immunity. These responses corresponded with significant increases in tumor-infiltrating lymphocytes and increased expression of lymphocyte-homing signals in the metastatic tumors. Furthermore, we demonstrated evidence of durable tumor-specific antitumor immunity. In conclusion, increasing LIGHT expression increased T-cell proliferation, activation, and infiltration, resulting in enhanced tumor-specific immune-mediated tumor regressions in primary tumors and colorectal liver metastases. Mechanisms to increase LIGHT in the colon cancer microenvironment warrant further investigation and hold promise as an immunotherapeutic strategy. Cancer Res; 77(8); 1880-91. ©2017 AACR. ©2017 American Association for Cancer Research.

  17. Choroidal metastases as the initial presentation of lung cancer: A ...

    African Journals Online (AJOL)

    Clinical reports of symptomatic intraocular metastasis as the initial presentation of lung cancer are rare. We report the case of a 49-year-old female patient who presented with loss of vision due to choroidal metastases as the initial manifestation of her disseminated lung cancer. This particular patient was referred to us from ...

  18. Choroidal Metastases as the Initial Presentation of Lung Cancer: A ...

    African Journals Online (AJOL)

    Clinical reports of symptomatic intraocular metastasis as the initial presentation of lung cancer are rare. We report the case of a 49-year-old female patient who presented with loss of vision due to choroidal metastases as the initial manifestation of her disseminated lung cancer. This particular patient was referred to us from.

  19. Multiple metastases from ovarian cancer | Singh | South African ...

    African Journals Online (AJOL)

    ... cancer will already have spread beyond the ovaries in approximately 75% of cases. We report a case of epithelial ovarian cancer presenting with liver and thoracic vertebral metastases 4 months after completion of treatment, as part of distant spread. The patient was then treated with gemcitabine-based chemotherapy.

  20. Radiofrequency ablation for pulmonary metastases from gastrointestinal cancers.

    Science.gov (United States)

    Baba, Yoshifumi; Watanabe, Masayuki; Yoshida, Naoya; Kawanaka, Koichi; Yamashita, Yasuyuki; Baba, Hideo

    2014-01-01

    The lung is one of the most common targets of metastases from gastrointestinal (GI) cancers. Surgical treatment (i.e., metastasectomy) is an accepted therapeutic option for pulmonary metastases from GI cancers. However, surgery may be contraindicated in advanced stages of cancer, compromised lung function, and/or comorbidities. This issue has prompted the search for innovative and less invasive ways of treating pulmonary metastases. Image-guided radiofrequency ablation (RFA) has attracted great interest as a minimally invasive approach against intrathoracic malignancies. In this technique, radiofrequency energy is applied via a needle electrode inserted into the target tissue. As the cells are agitated by the applied energy, they release heat, causing denaturation and cell death. Recently, this technique has been used on patients with pulmonary metastatic disease arising from GI cancers such as colorectal cancer, esophageal cancer, and hepatocellular carcinoma, as well as on patients with primary lung cancer. The present review updates the clinical outcomes and advances in RFA therapy of lung metastases from GI cancers.

  1. Review of Animal Models of Prostate Cancer Bone Metastasis

    Directory of Open Access Journals (Sweden)

    Jessica K. Simmons

    2014-06-01

    Full Text Available Prostate cancer bone metastases are associated with a poor prognosis and are considered incurable. Insight into the formation and growth of prostate cancer bone metastasis is required for development of new imaging and therapeutic strategies to combat this devastating disease. Animal models are indispensable in investigating cancer pathogenesis and evaluating therapeutics. Multiple animal models of prostate cancer bone metastasis have been developed, but few effectively model prostatic neoplasms and osteoblastic bone metastases as they occur in men. This review discusses the animal models that have been developed to investigate prostate cancer bone metastasis, with a focus on canine models and also includes human xenograft and rodent models. Adult dogs spontaneously develop benign prostatic hyperplasia and prostate cancer with osteoblastic bone metastases. Large animal models, such as dogs, are needed to develop new molecular imaging tools and effective focal intraprostatic therapy. None of the available models fully reflect the metastatic disease seen in men, although the various models have provided important insight into the metastatic process. As additional models are developed and knowledge from the different models is combined, the molecular mechanisms of prostate cancer bone metastasis can be deciphered and targeted for development of novel therapies and molecular diagnostic imaging.

  2. Three cases of bone metastases in patients with gastrointestinal stromal tumors

    Directory of Open Access Journals (Sweden)

    Maurizio Zompatori

    2011-04-01

    Full Text Available Gastrointestinal stromal tumors (GISTs are rare, but represent the most common mesenchymal neoplasms of the gastrointestinal tract. Tumor resection is the treatment of choice for localized disease. Tyrosine kinase inhibitors (imatinib, sunitinib are the standard therapy for metastatic or unresectable GISTs. GISTs usually metastasize to the liver and peritoneum. Bone metastases are uncommon. We describe three cases of bone metastases in patients with advanced GISTs: two women (82 and 54 years of age, and one man (62 years of age. Bones metastases involved the spine, pelvis and ribs in one patient, multiple vertebral bodies and pelvis in one, and the spine and iliac wings in the third case. The lesions presented a lytic pattern in all cases. Two patients presented with multiple bone metastases at the time of initial diagnosis and one patient after seven years during the follow-up period. This report describes the diagnosis and treatment of the lesions and may help clinicians to manage bones metastases in GIST patients.

  3. Modern Detection of Prostate Cancer's Bone Metastasis: Is the Bone Scan Era Over?

    Directory of Open Access Journals (Sweden)

    Bertrand Tombal

    2012-01-01

    Full Text Available Prostate cancer cells have an exquisite tropism for bone, which clinically translates into the highest rate of bone metastases amongst male cancers. Although in the latest years there has been an active development of new “bone targeted” therapies, modern diagnostic techniques for bone metastases still relies mostly on 99mTc bone scanning (BS and plain X-ray. BS dramatically lacks specificity and sensitivity. Recent publications using modern imaging technologies have clearly pinpointed that BS grossly underestimates the true prevalence of bone metastasis. In addition BS does not allow tumour measurement and is, therefore, not appropriate to monitor response to therapy. This might be extremely important in patients harbouring high-risk localized disease that are eventually candidate for local therapy. Here we reviewed what are the emerging imaging strategies that are likely to supplant BS and to what extent they can be used in the clinic already.

  4. Advances in neoadjuvant therapy for colorectal cancer with liver metastases.

    Science.gov (United States)

    Pozzo, Carmelo; Barone, Carlo; Kemeny, Nancy E

    2008-06-01

    Metastatic colorectal cancer (CRC) is most frequently seen in the liver. Resection of metastases remains the treatment of choice; however, the majority of patients are ineligible for surgery due to unfavorable location, size, or number of metastases; insufficient liver reserve; or extrahepatic disease. The activity of irinotecan- and oxaliplatin-based regimens as first-line therapy has prompted the investigation of these agents as neoadjuvant therapy in patients with resectable and unresectable disease. Although studies suggest considerable promise for a neoadjuvant strategy in patients with unresectable liver metastases, the heterogeneity, small size, and retrospective nature of many of these studies precludes drawing firm clinical conclusions at this time, especially in patients with resectable disease. Therefore large, prospective trials that examine the impact of preoperative chemotherapy in patients with initially unresectable or resectable liver metastases are needed. These trials must include well-defined criteria for resectability and clear reporting of the extent of resection.

  5. How MMPs Impact Bone Responses to Metastatic Prostate Cancer

    Science.gov (United States)

    2011-04-30

    Washington Note: Sup Cancer Res Correspon and Rehab Tower, Sui Fax: 615-3 doi: 10.115 ©2010 Am www.aacrIn human prostate to bone metastases and in a...threshold. The number of osteolytic lesions that completely penetrated the cortical bone, as seen in the virtual reconstruction, were counted. MicroCT...at the time of their death [1–3]. Bone metastases are often termed as either osteolytic or osteogenic but in reality , the lesions contain areas of

  6. Incidental detection of hyperfunctioning thyroid cancer metastases in patients presenting with thyrotoxicosis

    Directory of Open Access Journals (Sweden)

    Nishikant A Damle

    2012-01-01

    Full Text Available Thyrotoxicosis due to functioning metastases from thyroid cancer is rare. It also presents a therapeutic challenge, as both the metastatic cancer and thyrotoxicosis need to be treated. We present here two cases of thyrotoxicosis which on a routine 99m Tc-pertechnetate thyroid scan showed extrathyroidal foci of uptake. Two patients who initially presented with thyrotoxicosis underwent a routine thyroid scan. Abnormal uptake in the shoulder was incidentally noted, which prompted us to do a whole body pertechnetate scan in the same sitting, which revealed extensive hyperfunctioning metastases in the lungs and bones. We also discuss the ′Flip Flop′ phenomenon in thyroid cancer, which was seen in our case. This report emphasizes the importance of evaluating the abnormal foci of uptake seen on a routine thyroid scan.

  7. How I do it: managing bone health in patients with prostate cancer.

    Science.gov (United States)

    Barkin, Jack

    2014-08-01

    Urologists have two scenarios where they have to address bone loss or increased risk of fractures in men with prostate cancer. In the first setting, a patient who has been started on androgen deprivation therapy may develop cancer-treatment-induced bone loss. In the second setting, a patient's prostate cancer may have metastasized to the bone. This article describes six steps to manage bone health in patients diagnosed with prostate cancer in a community practice.

  8. Liver resection and local ablation of breast cancer liver metastases--a systematic review

    DEFF Research Database (Denmark)

    Bergenfeldt, M; Jensen, B V; Skjoldbye, B

    2011-01-01

    To analyze surgical treatment of breast cancer liver metastases (BCLM) regarding selection criteria, outcome and prognostic parameters.......To analyze surgical treatment of breast cancer liver metastases (BCLM) regarding selection criteria, outcome and prognostic parameters....

  9. Bone Cancer - Multiple Languages

    Science.gov (United States)

    ... Supplements Videos & Tools You Are Here: Home → Multiple Languages → All Health Topics → Bone Cancer URL of this page: https://medlineplus.gov/languages/bonecancer.html Other topics A-Z Expand Section ...

  10. Temporal Subtraction of Serial CT Images with Large Deformation Diffeomorphic Metric Mapping in the Identification of Bone Metastases.

    Science.gov (United States)

    Sakamoto, Ryo; Yakami, Masahiro; Fujimoto, Koji; Nakagomi, Keita; Kubo, Takeshi; Emoto, Yutaka; Akasaka, Thai; Aoyama, Gakuto; Yamamoto, Hiroyuki; Miller, Michael I; Mori, Susumu; Togashi, Kaori

    2017-11-01

    Purpose To determine the improvement of radiologist efficiency and performance in the detection of bone metastases at serial follow-up computed tomography (CT) by using a temporal subtraction (TS) technique based on an advanced nonrigid image registration algorithm. Materials and Methods This retrospective study was approved by the institutional review board, and informed consent was waived. CT image pairs (previous and current scans of the torso) in 60 patients with cancer (primary lesion location: prostate, n = 14; breast, n = 16; lung, n = 20; liver, n = 10) were included. These consisted of 30 positive cases with a total of 65 bone metastases depicted only on current images and confirmed by two radiologists who had access to additional imaging examinations and clinical courses and 30 matched negative control cases (no bone metastases). Previous CT images were semiautomatically registered to current CT images by the algorithm, and TS images were created. Seven radiologists independently interpreted CT image pairs to identify newly developed bone metastases without and with TS images with an interval of at least 30 days. Jackknife free-response receiver operating characteristics (JAFROC) analysis was conducted to assess observer performance. Reading time was recorded, and usefulness was evaluated with subjective scores of 1-5, with 5 being extremely useful and 1 being useless. Significance of these values was tested with the Wilcoxon signed-rank test. Results The subtraction images depicted various types of bone metastases (osteolytic, n = 28; osteoblastic, n = 26; mixed osteolytic and blastic, n = 11) as temporal changes. The average reading time was significantly reduced (384.3 vs 286.8 seconds; Wilcoxon signed rank test, P = .028). The average figure-of-merit value increased from 0.758 to 0.835; however, this difference was not significant (JAFROC analysis, P = .092). The subjective usefulness survey response showed a median score of 5 for use of the technique

  11. Multiparametric Magnetic Resonance Imaging of Prostate Cancer Bone Disease

    Science.gov (United States)

    Perez-Lopez, Raquel; Nava Rodrigues, Daniel; Figueiredo, Ines; Mateo, Joaquin; Collins, David J.; Koh, Dow-Mu; de Bono, Johann S.; Tunariu, Nina

    2018-01-01

    Objectives The aim of this study was to correlate magnetic resonance imaging (MRI) of castration-resistant prostate cancer (CRPC) bone metastases with histological and molecular features of bone metastases. Materials and Methods Forty-three bone marrow biopsies from 33 metastatic CRPC (mCRPC) patients with multiparametric MRI and documented bone metastases were evaluated. A second cohort included 10 CRPC patients with no bone metastases. Associations of apparent diffusion coefficient (ADC), normalized b900 diffusion-weighted imaging (nDWI) signal, and signal-weighted fat fraction (swFF) with bone marrow biopsy histological parameters were evaluated using Mann-Whitney U test and Spearman correlations. Univariate and multivariate logistic regression models were analyzed. Results Median ADC and nDWI signal was significantly higher, and median swFF was significantly lower, in bone metastases than nonmetastatic bone (P < 0.001). In the metastatic cohort, 31 (72.1%) of 43 biopsies had detectable cancer cells. Median ADC and swFF were significantly lower and median nDWI signal was significantly higher in biopsies with tumor cells versus nondetectable tumor cells (898 × 10−6 mm2/s vs 1617 × 10−6 mm2/s; 11.5% vs 62%; 5.3 vs 2.3, respectively; P < 0.001). Tumor cellularity inversely correlated with ADC and swFF, and positively correlated with nDWI signal (P < 0.001). In serial biopsies, taken before and after treatment, changes in multiparametric MRI parameters paralleled histological changes. Conclusions Multiparametric MRI provides valuable information about mCRPC bone metastases. These data further clinically qualify DWI as a response biomarker in mCRPC. PMID:28906339

  12. Breast Cancer and Bone Loss

    Science.gov (United States)

    ... Menopause Map Featured Resource Find an Endocrinologist Search Breast Cancer and Bone Loss July 2010 Download PDFs English ... G. Komen Foundation What is the link between breast cancer and bone loss? Certain treatments for breast cancer ...

  13. Outcomes of uterine cervical cancer patients with pelvic lymph node metastases after radiotherapy without boost irradiation of metastases.

    Science.gov (United States)

    Yoshizawa, Eriko; Koiwai, Keiichiro; Ina, Hironobu; Fukazawa, Ayumu; Sakai, Katsuya; Ozawa, Takesumi; Matsushita, Hirohide; Kadoya, Masumi

    2017-04-01

    The aim of this study was to evaluate the outcomes of uterine cervical cancer patients with pelvic lymph node (PLN) metastases after radiotherapy without boost irradiation of the metastases and to clarify the necessity of the boost irradiation of metastatic lesions. Thirty-two patients with uterine cervical cancer metastasizing only to the PLN were treated with definitive radiotherapy without boost irradiation of the metastases between 2008 and 2012 at our institution and were selected for this study. The pattern of progression, overall survival, and progression-free survival were analyzed. Ninety percent of the PLN metastases were controlled by radiotherapy. Twenty-two of 32 patients (69%) experienced progression. Distant metastases as initial progression were observed in 21 of these 22 patients (95%). Only two patients experienced failures in pre-treatment metastatic PLN as initial progression, along with other failures. Severe late lower gastrointestinal toxicities were not observed in any patients. Two-year cumulative overall survival and progression-free survival were 74% and 31%, respectively. Boost irradiation of PLN metastases is not necessarily indispensable. Further studies to examine the necessity of boost irradiation of PLN metastases in radiotherapy for uterine cervical cancer patients with metastases are required. © 2017 Japan Society of Obstetrics and Gynecology.

  14. FDG-PET/CT-guided biopsy of bone metastases sets a new course in patient management after extensive imaging and multiple futile biopsies.

    Science.gov (United States)

    Werner, M K; Aschoff, P; Reimold, M; Pfannenberg, C

    2011-03-01

    A 73-year-old man with a history of prostate and bladder carcinoma and persistent back pain was diagnosed by MRI with multiple vertebral metastases including a compression fracture of T7. He received radiotherapy for pain relief and for vertebral instability with incipient spinal stenosis, but additional targeted systemic therapy was intended. Therefore, multiple attempts at minimally invasive and open biopsies for histological characterisation of the bone metastases were performed, but failed to provide a conclusive specimen, although CT, MRI and bone scintigraphy were used for biopsy planning. Only histopathological analysis of an (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT-guided additional biopsy at a site with high metabolic activity yielded the final diagnosis of bone metastases of a neuroendocrine small cell cancer of unknown origin; hence, the patient had a third malignancy requiring a different therapy regimen and diagnostic work-up.

  15. Bone marrow micrometastasis detected by flow cytometry is associated bone, bone marrow, lung macrometastasis in breast cancer

    Directory of Open Access Journals (Sweden)

    Mustafa Salih Akin

    2014-04-01

    Material and Methods: Bone marrow samples were obtained from 52 breast cancer patients and 16 control patients via aspiration from the iliac spine at the time of first diagnosis after the surgery. Epithelial cells were identified with anti-cytokeratin monoclonal antibody, and double-staining with propidium iodide and CD45using flow cytometry. Results: In all, 2 (12.5% of the 16 control patients and 11 (21% of the 52 breast cancer patients had cytokeratin-18 positive cells in their bone marrow. A relationship between the presence of occult metastatic cells in bone marrow, and the presence/absence of lymph node metastases, tumor size, stage, menopausal status, hormone receptor status, histological grade, c-erb-B2 expression, tumor subtype, lymphovascular invasion, Ductal carcinoma in situ (DCIS component, and gender was not observed. Significant positive relationships were observed between bone marrow micrometastasis, and age, and bone, bone marrow, lung, and liver metastases. Conclusion: Bone marrow micrometastasis was associated with age, bone, bone marrow, lung, and liver metastases at the time of diagnosis.. [Cukurova Med J 2014; 39(2.000: 305-314

  16. Apolipoprotein D expression in metastasic lymph nodes of breast cancer.

    Science.gov (United States)

    Lamelas, M L; Vázquez, J; Enguita, M I; Rodríguez, J C; González, L O; Merino, A M; Vizoso, F

    2000-01-01

    Apolipoprotein D is a glycoprotein of the human plasma whose functional role remains unclear. On the other hand, this protein is also produced by breast carcinomas and is positively associated with a favorable outcome of patients. However, none study has focused on metastasic lesions. To analyze apolipoprotein D expression in breast cancer patients and their synchronous metastasic axillary lymph nodes. We analyzed by immunohistochemical assay both, the tumoral expression of apolipoprotein D in primary tumors and in their synchronous metastasic axillary lymph nodes of 30 node-positive breast cancer patients. Of the primary tumors, 28 (93.3%) showed a positive immunostaining for apolipoprotein D, although there was wide variability immunostaining values. On the other hand, 16 (53.3%) patients showed a positive immunostaining for the protein in their tumoral lymph nodes. In addition, there was a significant positive relationship between the tumoral expression of apolipoprotein D in primary tumors and metastasic lymph nodes (P metastasic lymph nodes of breast carcinomas, but with a different pattern of immunostaining and less clinical significance than in primary tumors.

  17. Lung cancer revealed by multiple metastases of the scalp | Fetohi ...

    African Journals Online (AJOL)

    Skin metastases of lung cancer are rare. They are symptoms of progressive disease and usually a sign of a poor prognosis. We report a case of 69-years-old man with no significant medical history, never smoker, which consulted a dermatologist for scalp nodules that appeared for more than 16 months in the scalp and ...

  18. Clinical and molecular complexity of breast cancer metastases.

    Science.gov (United States)

    Kimbung, Siker; Loman, Niklas; Hedenfalk, Ingrid

    2015-12-01

    Clinical oncology is advancing toward a more personalized treatment orientation, making the need to understand the biology of metastasis increasingly acute. Dissecting the complex molecular, genetic and clinical phenotypes underlying the processes involved in the development of metastatic disease, which remains the principal cause of cancer-related deaths, could lead to the identification of more effective prognostication and targeted approaches to prevent and treat metastases. The past decade has witnessed significant progress in the field of cancer metastasis research. Clinical and technological milestones have been reached which have tremendously enriched our understanding of the complex pathways undertaken by primary tumors to progress into lethal metastases and how some of these processes might be amenable to therapy. The aim of this review article is to highlight the recent advances toward unraveling the clinical and molecular complexity of breast cancer metastases. We focus on genes mediating breast cancer metastases and organ-specific tropism, and discuss gene signatures for prediction of metastatic disease. The challenges of translating this information into clinically applicable tools for improving the prognostication of the metastatic potential of a primary breast tumor, as well as for therapeutic interventions against latent and active metastatic disease are addressed. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  19. Ganging Up on Brain Metastases | Center for Cancer Research

    Science.gov (United States)

    When primary tumors metastasize to the brain, the prognosis for patients is poor. The currently accepted treatment is whole-brain radiation therapy, and the median survival time is several months. Since these types of tumors form in 10 to 30 percent of adult cancer patients, improvements in treatment methods are a necessity.  

  20. Hepatocyte Growth Factor and Interleukin-6 in Prostate Cancer Bone Metastasis

    National Research Council Canada - National Science Library

    Knudsen, Beatrice

    2004-01-01

    The hypothesis of this grant proposal is that androgen-ablative therapy paradoxically increases growth factor secretion from bone stromal cells and that this may stimulate the growth of prostate cancer metastases...

  1. Hepatocyte Growth Factor and Interleukin-6 in Prostate Cancer Bone Metastasis

    National Research Council Canada - National Science Library

    Knudsen, Beatrice S

    2006-01-01

    The hypothesis of this grant proposal is that androgen-ablative therapy paradoxically increases growth factor secretion from bone stromal cells and that this may stimulate the growth of prostate cancer metastases...

  2. Bone metastases from renal cell carcinoma: patient survival after surgical treatment

    Directory of Open Access Journals (Sweden)

    Baur-Melnyk Andrea

    2010-07-01

    Full Text Available Abstract Background Surgery is the primary treatment of skeletal metastases from renal cell carcinoma, because radiation and chemotherapy frequently are not effecting the survival. We therefore explored factors potentially affecting the survival of patients after surgical treatment. Methods We retrospectively reviewed 101 patients operatively treated for skeletal metastases of renal cell carcinoma between 1980 and 2005. Overall survival was calculated using the Kaplan-Meier method. The effects of different variables were evaluated using a log-rank test. Results 27 patients had a solitary bone metastasis, 20 patients multiple bone metastases and 54 patients had concomitant visceral metastases. The overall survival was 58% at 1 year, 37% at 2 years and 12% at 5 years. Patients with solitary bone metastases had a better survival (p Conclusions The data suggest that patients with a solitary metastasis or a limited number of resectable metastases are candidates for wide resections. As radiation and chemotherapy are ineffective in most patients, surgery is a better option to achieve local tumor control and increase the survival.

  3. SU-F-T-57: Delivered Activity Accuracy of Radium 223 Dichloride Injections, When Being Administrated for Castration Resistant Prostate Cancer, Symptomatic Bone Metastases. The Impact of Residual Activity in the Spent Syringe and Dispensing Accuracy of Ra 223

    Energy Technology Data Exchange (ETDEWEB)

    Jennings, G [Marsden Medical Physics Associates, Denville, NJ (United States)

    2016-06-15

    Purpose: To quantify the delivered activity accuracy of Radium 223 dichloride injections, when being administrated for castration – resistant prostate cancer, symptomatic bone metastases. The impact of residual activity in the spent syringe and dispensing accuracy of Ra 223. Methods: The administration is by slow intravenous injection over 1 minute followed by double flushing of the 10 mL syringe and IV with saline. Eighty (80) procedures was used to investigate variations in the activity from the amount prescribed (µCi) = 1.35 × Patient weight Kg. The Activity dispensed into a 10mL syringe using a NIST traceable Capintec CRC-25R Chamber and a cross calibrated capintec CRC-15R to measure activity in the syringe immediately before and after administration Results: The patients weight range from 121Ib to 235lb and doses ranging 74.25 µCi to 144.2 µCi. The deviation of dispensed dose vs Prescribed dose average +2.1% with a range of −1.1% to +5.7%. The Dose measured before administration ranges 79.3 µCi to 154.9 µCi. Deviation from the dispensed dose was show to average +2.9% with a range of −0.8% to +7.3%. The average residual dose post injection was 2.5 µCi or 2.2% of the pre injection activity. Ranging from 0.9 µCi to 6.2 µCi, 0.7% to 5.4% respectively. Subtracting the residual activity from that measured activity before injection and comparing it to prescription dose was shown to have an average variation of +2.7% with a range of −0.8% to 7.4%. Conclusion: The case resulted in the 6.2 µCi maximum residual dose had two syringes. A small, 82.8 µCi activity, case resulted in the 7.4% maximum variation in measures less residual verses prescription dose. The average +2.1 % dispenses activity of Ra 223 over the prescription dosage was seen to counteract the average 2.2% residual dosage found to remain in the syringe.

  4. Upregulation of Claudin-4, CAIX and GLUT-1 in distant breast cancer metastases.

    Science.gov (United States)

    Jiwa, Laura S; van Diest, Paul J; Hoefnagel, Laurien D; Wesseling, Jelle; Wesseling, Pieter; Moelans, Cathy B

    2014-11-22

    Several studies have shown that the immunophenotype of distant breast cancer metastases may differ significantly from that of the primary tumor, especially with regard to differences in the level of hormone receptor protein expression, a process known as receptor conversion. This study aimed to compare expression levels of several membrane proteins between primary breast tumors and their corresponding distant metastases in view of their potential applicability for molecular imaging and drug targeting. Expression of Claudin-4, EGFR, CAIX, GLUT-1 and IGF1R was assessed by immunohistochemistry on tissue microarrays composed of 97 paired primary breast tumors and their distant (non-bone) metastases. In both the primary cancers and the metastases, Claudin-4 was most frequently expressed, followed by GLUT-1, CAIX and EGFR.From primary breast cancers to their distant metastases there was positive to negative conversion, e.g. protein expression in the primary tumor with no expression in its paired metastasis, in 6%, 19%, 12%, 38%, and 0% for Claudin-4 (n.s), GLUT-1 (n.s), CAIX (n.s), EGFR (n.s) and IGF1R (n.s) respectively. Negative to positive conversion was seen in 65%, 47%, 43%, 9% and 0% of cases for Claudin-4 (p = 0.049), GLUT-1 (p = 0.024), CAIX (p = 0.002), EGFR (n.s.) and IGF1R (n.s.) respectively. Negative to positive conversion of Claudin-4 in the metastasis was significantly associated with tumor size (p = 0.015), negative to positive conversion of EGFR with negative PR status (p = 0.046) and high MAI (p = 0.047) and GLUT-1 negative to positive conversion with (neo)adjuvant chemotherapy (p = 0.039) and time to metastasis formation (p = 0.034). CAIX and GLUT-1 expression in the primary tumor were significantly associated with high MAI (p = 0.008 and p = 0.038 respectively). Claudin-4 is frequently expressed in primary breast cancers but especially in their metastases and is thereby an attractive membrane bound molecular imaging and drug target. Conversion in

  5. Radioiodine therapy in skeletal metastases from well-differentiated thyroid cancer: a Johannesburg experience

    Directory of Open Access Journals (Sweden)

    Nalini Sindy Perumal

    2010-03-01

    Full Text Available Aim.The purpose of this study was to examine the outcome of patients with skeletal metastases from well-differentiated thyroid carcinoma and analyse the effect of variables that influence the prognosis of this disease. Method. We retrospectively reviewed 352 patients treated and followed-up at the Charlotte Maxeke Johannesburg Academic Hospital’s thyroid cancer clinic from 1982 - 1999. Findings. Skeletal metastases were diagnosed in 24 (6.8%, 17 at presentation to the thyroid clinic, and 7 at follow-up. Patients’ ages ranged from 30 - 77 years (mean 53.9 years and the female:male ratio was 3.8:1. Based on the original pathology reports from resected tumours, 9 were papillary and 15 were follicular cancers. Twenty-three of the 24 patients underwent thyroid surgery as the initial management – total thyroidectomy in 18, subtotal thyroidectomy in 3, and lobectomy plus neck dissection in one. The diagnosis of thyroid cancer was based on lobectomy in a single subject. Radioactive iodine (RAI was used as part of the original treatment; external radiation therapy (XRT was mainly used to alleviate severe symptoms. Twenty-one patients (87.5% were treated with RAI; 11 (45.8% received radiotherapy. Seven patients died – 4 from neurological disease directly associated with bone metastases. Of the 17 surviving patients, 2 appeared to be disease-free, 8 were asymptomatic despite overt bony disease, and 7 had persistent symptoms which much improved in 5. Bone metastases were uncommon, and follicular cancer predominated in this survey. Conclusion. RAI therapy improves quality of life in most patients. There is a place for XRT.

  6. From Prostate to Bone: Key Players in Prostate Cancer Bone Metastasis

    Directory of Open Access Journals (Sweden)

    Megan N. Thobe

    2011-01-01

    Full Text Available Bone is the most common site for metastasis in human prostate cancer patients. Skeletal metastases are a significant cause of morbidity and mortality and overall greatly affect the quality of life of prostate cancer patients. Despite advances in our understanding of the biology of primary prostate tumors, our knowledge of how and why secondary tumors derived from prostate cancer cells preferentially localize bone remains limited. The physiochemical properties of bone, and signaling molecules including specific chemokines and their receptors, are distinct in nature and function, yet play intricate and significant roles in prostate cancer bone metastasis. Examining the impact of these facets of bone metastasis in vivo remains a significant challenge, as animal models that mimic the natural history and malignant progression clinical prostate cancer are rare. The goals of this article are to discuss (1 characteristics of bone that most likely render it a favorable environment for prostate tumor cell growth, (2 chemokine signaling that is critical in the recruitment and migration of prostate cancer cells to the bone, and (3 current animal models utilized in studying prostate cancer bone metastasis. Further research is necessary to elucidate the mechanisms underlying the extravasation of disseminated prostate cancer cells into the bone and to provide a better understanding of the basis of cancer cell survival within the bone microenvironment. The development of animal models that recapitulate more closely the human clinical scenario of prostate cancer will greatly benefit the generation of better therapies.

  7. From Prostate to Bone: Key Players in Prostate Cancer Bone Metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Thobe, Megan N. [Section of Urology, Department of Surgery, The University of Chicago, Chicago, IL 60637 (United States); Clark, Robert J. [Department of Molecular Pathogenesis and Molecular Medicine, The University of Chicago, Chicago, IL 60637 (United States); Bainer, Russell O. [Department of Human Genetics, The University of Chicago, Chicago, IL 60637 (United States); Prasad, Sandip M.; Rinker-Schaeffer, Carrie W., E-mail: crinkers@uchicago.edu [Section of Urology, Department of Surgery, The University of Chicago, Chicago, IL 60637 (United States)

    2011-01-27

    Bone is the most common site for metastasis in human prostate cancer patients. Skeletal metastases are a significant cause of morbidity and mortality and overall greatly affect the quality of life of prostate cancer patients. Despite advances in our understanding of the biology of primary prostate tumors, our knowledge of how and why secondary tumors derived from prostate cancer cells preferentially localize bone remains limited. The physiochemical properties of bone, and signaling molecules including specific chemokines and their receptors, are distinct in nature and function, yet play intricate and significant roles in prostate cancer bone metastasis. Examining the impact of these facets of bone metastasis in vivo remains a significant challenge, as animal models that mimic the natural history and malignant progression clinical prostate cancer are rare. The goals of this article are to discuss (1) characteristics of bone that most likely render it a favorable environment for prostate tumor cell growth, (2) chemokine signaling that is critical in the recruitment and migration of prostate cancer cells to the bone, and (3) current animal models utilized in studying prostate cancer bone metastasis. Further research is necessary to elucidate the mechanisms underlying the extravasation of disseminated prostate cancer cells into the bone and to provide a better understanding of the basis of cancer cell survival within the bone microenvironment. The development of animal models that recapitulate more closely the human clinical scenario of prostate cancer will greatly benefit the generation of better therapies.

  8. A core program of gene expression characterizes cancer metastases.

    Science.gov (United States)

    Hartung, Franz; Wang, Yunguan; Aronow, Bruce; Weber, Georg F

    2017-11-24

    While aberrant expression or splicing of metastasis genes conveys to cancers the ability to break through tissue barriers and disseminate, the genetic basis for organ preference in metastasis formation has remained incompletely understood. Utilizing the gene expression profiles from 653 GEO datasets, we investigate whether the signatures by diverse cancers in various metastatic sites display common features. We corroborate the meta-analysis in a murine model. Metastases are generally characterized by a core program of gene expression that induces the oxidative metabolism, activates vascularization/tissue remodeling, silences extracellular matrix interactions, and alters ion homeostasis. This program distinguishes metastases from their originating primary tumors as well as from their target host tissues. Site-selectivity is accomplished through specific components that adjust to the target micro-environment. The same functional groups of gene expression programs are activated in the metastases of B16-F10 cells to various target organs. It remains to be investigated whether these genetic signatures precede implantation and thus determine organ preference or are shaped by the target site and are thus a consequence of implantation. Conceivably, chemotherapy of disseminated cancer might be more efficacious if selected to match the genetic makeup of the metastases rather than the organ of origin by the primary tumor.

  9. Tumor-expressed adrenomedullin accelerates breast cancer bone metastasis.

    Science.gov (United States)

    Siclari, Valerie A; Mohammad, Khalid S; Tompkins, Douglas R; Davis, Holly; McKenna, C Ryan; Peng, Xianghong; Wessner, Lisa L; Niewolna, Maria; Guise, Theresa A; Suvannasankha, Attaya; Chirgwin, John M

    2014-12-02

    Adrenomedullin (AM) is secreted by breast cancer cells and increased by hypoxia. It is a multifunctional peptide that stimulates angiogenesis and proliferation. The peptide is also a potent paracrine stimulator of osteoblasts and bone formation, suggesting a role in skeletal metastases-a major site of treatment-refractory tumor growth in patients with advanced disease. The role of adrenomedullin in bone metastases was tested by stable overexpression in MDA-MB-231 breast cancer cells, which cause osteolytic bone metastases in a standard animal model. Cells with fivefold increased expression of AM were characterized in vitro, inoculated into immunodeficient mice and compared for their ability to form bone metastases versus control subclones. Bone destruction was monitored by X-ray, and tumor burden and osteoclast numbers were determined by quantitative histomorphometry. The effects of AM overexpression on tumor growth and angiogenesis in the mammary fat pad were determined. The effects of AM peptide on osteoclast-like multinucleated cell formation were tested in vitro. A small-molecule AM antagonist was tested for its effects on AM-stimulated ex vivo bone cell cultures and co-cultures with tumor cells, where responses of tumor and bone were distinguished by species-specific real-time PCR. Overexpression of AM mRNA did not alter cell proliferation in vitro, expression of tumor-secreted factors or cell cycle progression. AM-overexpressing cells caused osteolytic bone metastases to develop more rapidly, which was accompanied by decreased survival. In the mammary fat pad, tumors grew more rapidly with unchanged blood vessel formation. Tumor growth in the bone was also more rapid, and osteoclasts were increased. AM peptide potently stimulated bone cultures ex vivo; responses that were blocked by small-molecule adrenomedullin antagonists in the absence of cellular toxicity. Antagonist treatment dramatically suppressed tumor growth in bone and decreased markers of

  10. The incidence of bone metastasis after early-stage breast cancer in Canada.

    Science.gov (United States)

    Liede, Alexander; Jerzak, Katarzyna J; Hernandez, Rohini K; Wade, Sally W; Sun, Ping; Narod, Steven A

    2016-04-01

    Current information on the incidence and prevalence of bone metastases in women with breast cancer is scarce. This study examined the occurrence and predictors of bone metastases, as well as post-metastasis survival in a prospective cohort of Canadian women with breast cancer. We included women treated for early-stage (stage I, II, or III) breast cancer at the Henrietta Banting Breast Centre (HBBC) in Toronto, Canada between 1987 and 2000. Data were abstracted from medical records and pathology reports in the HBBC database; follow-up extended to end of data availability or August 31, 2015. Actuarial survival analyses provided cumulative incidence of bone metastases at 5, 10, and 15 years after breast cancer diagnosis. Kaplan-Meier curves describe breast cancer mortality. Regression models assessed patient, tumor, and treatment characteristics as predictors of bone metastases with all-cause mortality as a competing risk. Among 2097 women studied, the 5-, 10-, and 15-year probability of bone metastasis was 6.5, 10.3, and 11.3 % for the first recurrence, and 8.4, 12.5, and 13.6 % for any bone recurrence. At median follow-up (12.5 years), 13.2 % of patients had bone metastases. Median survival was 1.6 years following bone metastasis, and shorter if both bone and visceral metastases occurred. Advanced age and adjuvant treatment with tamoxifen were protective against bone metastasis. In this representative cohort of women diagnosed with early-stage breast cancer in Ontario, Canada, with long follow-up, the incidence of bone metastases was consistent with longitudinal studies from the United Kingdom, Denmark, and the US.

  11. Sentinel Lymph Node Occult Metastases Have Minimal Survival Effect in Some Breast Cancer Patients

    Science.gov (United States)

    Detailed examination of sentinel lymph node tissue from breast cancer patients revealed previously unidentified metastases in about 16% of the samples, but the difference in 5-year survival between patients with and without these metastases was very small

  12. Gastric metastases mimicking primary gastric cancer: A brief literature review

    Directory of Open Access Journals (Sweden)

    Simona Gurzu

    2017-01-01

    Full Text Available Gastric cancer is the fifth most common cancer worldwide, with most cases presenting in the form of primary tumors. In this paper, we performed a literature review on the incidence and particularities of extragastric metastases. These lesions are rare in clinical practice and can be misdiagnosed as primary undifferentiated gastric carcinomas as the differential diagnosis between primary and secondary malignancy is difficult to make. As per the literature, the most common malignancies which can present gastric metastases are lung cancer, followed by carcinoma of the breast, esophagus, kidney, and head and neck carcinomas. Malignant melanoma, ovarian cancer, prostate cancer, and adrenal gland carcinomas are rarely described as presenting metastases in the stomach. In most cases, the literature addressed poorly differentiated tumors with high-grade malignancy. The most common feature was the ulcerated tumor with depressed area, associated with identifiable extragastric tumor cells in the gastric submucosa. The linitis plastica-like feature is unusual and is more characteristic of breast lobular carcinoma. The accurate diagnosis of such rare extragastric metastatic cases depends on the appropriate clinical history and precise pathological diagnosis, which is mandatory for initiating the best therapeutic options.

  13. Comparative analysis of 11 different radioisotopes for palliative treatment of bone metastases by computational methods

    Energy Technology Data Exchange (ETDEWEB)

    Guerra Liberal, Francisco D. C., E-mail: meb12020@fe.up.pt, E-mail: adriana-tavares@msn.com; Tavares, Adriana Alexandre S., E-mail: meb12020@fe.up.pt, E-mail: adriana-tavares@msn.com; Tavares, João Manuel R. S., E-mail: tavares@fe.up.pt [Instituto de Engenharia Mecânica e Gestão Industrial, Faculdade de Engenharia, Universidade do Porto, Rua Dr. Roberto Frias s/n, Porto 4200-465 (Portugal)

    2014-11-01

    Purpose: Throughout the years, the palliative treatment of bone metastases using bone seeking radiotracers has been part of the therapeutic resources used in oncology, but the choice of which bone seeking agent to use is not consensual across sites and limited data are available comparing the characteristics of each radioisotope. Computational simulation is a simple and practical method to study and to compare a variety of radioisotopes for different medical applications, including the palliative treatment of bone metastases. This study aims to evaluate and compare 11 different radioisotopes currently in use or under research for the palliative treatment of bone metastases using computational methods. Methods: Computational models were used to estimate the percentage of deoxyribonucleic acid (DNA) damage (fast Monte Carlo damage algorithm), the probability of correct DNA repair (Monte Carlo excision repair algorithm), and the radiation-induced cellular effects (virtual cell radiobiology algorithm) post-irradiation with selected particles emitted by phosphorus-32 ({sup 32}P), strontium-89 ({sup 89}Sr), yttrium-90 ({sup 90}Y ), tin-117 ({sup 117m}Sn), samarium-153 ({sup 153}Sm), holmium-166 ({sup 166}Ho), thulium-170 ({sup 170}Tm), lutetium-177 ({sup 177}Lu), rhenium-186 ({sup 186}Re), rhenium-188 ({sup 188}Re), and radium-223 ({sup 223}Ra). Results: {sup 223}Ra alpha particles, {sup 177}Lu beta minus particles, and {sup 170}Tm beta minus particles induced the highest cell death of all investigated particles and radioisotopes. The cell survival fraction measured post-irradiation with beta minus particles emitted by {sup 89}Sr and {sup 153}Sm, two of the most frequently used radionuclides in the palliative treatment of bone metastases in clinical routine practice, was higher than {sup 177}Lu beta minus particles and {sup 223}Ra alpha particles. Conclusions: {sup 223}Ra and {sup 177}Lu hold the highest potential for palliative treatment of bone metastases of all

  14. [Isolated splenic metastases from cervical cancer: a rare entity].

    Science.gov (United States)

    Villalón-López, José Sebastián; Souto-del Bosque, Rosalía; Montañez-Lugo, Juan Ignacio; Chávez-González, Bruno

    2014-01-01

    Splenic metastases from solid tumors are a rare event with an incidence of only 2.9% to 9%. Splenic metastases from cervical cancer are a rare entity. Only a few cases have been reported of isolated spleen metastases from cervical cancer. We present the case of a 76-year-old woman with moderately differentiated endocervical adenocarcinoma stromal and endocervical invasion. Clinical stage was Ib1 and Ca-125 values of 150 U. She was managed with hysterectomy and pelvic lymphadenectomy. She received pelvic radiotherapy (45 Gy) followed 24 Gy of brachytherapy. Two years later she presented with abdominal pain. Abdominal computed tomography showed two splenic parenchymal lesions without disease in the remainder of the abdominal cavity and chest with a Ca-125 of 2,733 U. The patient is submitted to splenectomy. Histopathology demonstrates splenic metastases of well-differentiated adenocarcinoma from the endocervix. Immunohistochemical stain showed positivity from carcinoembryonic antigen; estrogen and progesterone receptors are negative. Ca-125 level 8 weeks after surgery was 16 U/ml. The patient received six cycles of adjuvant chemotherapy with paclitaxel and cisplatin. At 12 months follow-up the patient is alive and without evidence of tumor activity. The spleen is an uncommon site of metastasis. Splenectomy is considered the appropriate treatment in order to avoid complications such as splenic rupture and splenic vein thrombosis as well as to improve pain control from splenomegaly. Twelve months after surgery our patient is alive and without evidence of tumor activity.

  15. Survival after bone metastasis by primary cancer type

    DEFF Research Database (Denmark)

    Svensson, Elisabeth; Christiansen, Christian F; Ulrichsen, Sinna P

    2017-01-01

    between 1994 and 2010, subsequently diagnosed with BM until 2012. We followed patients from date of bone metastasis diagnosis until death, emigration or 31 December 2012, whichever came first. We computed 1-year, 3-year and 5-year survival (%) and the corresponding 95% CIs stratified on primary cancer...... type. Comparing patients with bone metastasis only and patients with other synchronous metastases, we estimated crude and adjusted HRs and corresponding 95% CI for mortality. RESULTS: We included 17 251 patients with bone metastasis. The most common primary cancer types with bone metastasis were...... prostate (34%), breast (22%) and lung (20%). One-year survival after bone metastasis diagnosis was lowest in patients with lung cancer (10%, 95% CI 9% to 11%) and highest in patients with breast cancer (51%, 50% to 53%). At 5 years of follow-up, only patients with breast cancer had over 10% survival (13...

  16. Fractionation of Palliative Radiation Therapy for Bone Metastases in Ontario: Do Practice Guidelines Guide Practice?

    Energy Technology Data Exchange (ETDEWEB)

    Ashworth, Allison [Division of Cancer Care and Epidemiology, Queen' s Cancer Research Institute, Queen' s University, Kingston, Ontario (Canada); Cancer Center of Southeastern Ontario, Kingston, Ontario (Canada); Kong, Weidong [Division of Cancer Care and Epidemiology, Queen' s Cancer Research Institute, Queen' s University, Kingston, Ontario (Canada); Chow, Edward [Sunnybrook Regional Cancer Centre, Toronto, Ontario (Canada); Mackillop, William J., E-mail: william.mackillop@krcc.on.ca [Division of Cancer Care and Epidemiology, Queen' s Cancer Research Institute, Queen' s University, Kingston, Ontario (Canada); Cancer Center of Southeastern Ontario, Kingston, Ontario (Canada)

    2016-01-01

    Purpose: To evaluate the effect of a provincial practice guideline on the fractionation of palliative radiation therapy for bone metastases (PRT.B) in Ontario. Methods and Materials: The present retrospective study used electronic treatment records linked to Ontario's population-based cancer registry. Hierarchical multivariable regression analysis was used to evaluate temporal trends in the use of single fractions (SFs), controlling for patient-related factors associated with the use of SFs. Results: From 1984 to 2012, 43.9% of 161,835 courses of PRT.B were administered as SFs. The percentage of SF courses was greater for older patients (age <50 years, 39.8% vs age >80 years, 52.5%), those with a shorter life expectancy (survival >12 months, 36.9% vs < 1 month, 53.6%), and those who lived farther from a radiation therapy center (<10 km, 42.1% vs > 50 km, 47.3%). The percentage of SFs to spinal fields was lower than that to other skeletal sites (31.5% vs 57.1%). The percentage of SFs varied among the cancer centers (range, 26.0%-67.8%). These differences were all highly significant in the multivariable analysis (P<.0001). In 2004, Cancer Care Ontario released a practice guideline endorsing the use of SFs for uncomplicated bone metastases. The rate of use of SFs increased from 42.3% in the pre-guideline period (1999-2003) to 52.6% in the immediate post-guideline period (2004-2007). However, it subsequently decreased again to 44.0% (2009-2012). These temporal trends were significant after controlling for patient-related factors in the multivariable analysis (P<.0001). Large intercenter variations in the use of SFs persisted after publication of the guideline. Conclusions: The publication of an Ontario practice guideline endorsing the use of SF PRT.B was associated with only a transient increase in the use of SFs in Ontario and did little to reduce intercenter variations in fractionation.

  17. From palliative therapy to prolongation of survival: (223)RaCl2 in the treatment of bone metastases.

    Science.gov (United States)

    Liepe, Knut; Shinto, Ajit

    2016-07-01

    Patients with hormone-refractory prostate cancer often have multiple bone metastases. The resulting bone pain is associated with reduced life quality, increased cost of therapy and impairment of overall survival. Trials with bone-targeting β-emitters have mostly showed an effect on alleviation of bone pain along with prolongation in survival, documented in only a limited number of patients. A randomized phase III trial (ALSYMPCA) using the α-emitter (223)RaCl2 (Xofigo®) showed for the first time, a longer overall survival of 3.6 months in treated patients as a sign of an antitumor effect. The time to first skeletal-related events was also significantly longer in the therapy group compared with placebo. Because of the short range of α-emitter, the bone marrow toxicity of radium therapy is low, and so this radionuclide could also be a candidate for combination with chemotherapy. The elimination of (223)RaCl2 is mainly through the gastrointestinal tract and side effects are mainly in this area. The procedure is similar to treatment with other bone-seeking agents and consists of six administrations of 50 kBq/kg bodyweight Xofigo®, repeated every 4 weeks. At present Xofigo® is only approved for hormone-refractory prostate cancer.

  18. Inhibition of mammary tumor growth and metastases to bone and liver by dietary grape polyphenols.

    Science.gov (United States)

    Castillo-Pichardo, Linette; Martínez-Montemayor, Michelle M; Martínez, Joel E; Wall, Kristin M; Cubano, Luis A; Dharmawardhane, Suranganie

    2009-01-01

    The cancer preventive properties of grape products such as red wine have been attributed to polyphenols enriched in red wine. However, much of the studies on cancer preventive mechanisms of grape polyphenols have been conducted with individual compounds at concentrations too high to be achieved via dietary consumption. We recently reported that combined grape polyphenols at physiologically relevant concentrations are more effective than individual compounds at inhibition of ERalpha(-), ERbeta(+) MDA-MB-231 breast cancer cell proliferation, cell cycle progression, and primary mammary tumor growth (Schlachterman et al., Transl Oncol 1:19-27, 2008). Herein, we show that combined grape polyphenols induce apoptosis and are more effective than individual resveratrol, quercetin, or catechin at inhibition of cell proliferation, cell cycle progression, and cell migration in the highly metastatic ER (-) MDA-MB-435 cell line. The combined effect of dietary grape polyphenols (5 mg/kg each resveratrol, quercetin, and catechin) was tested on progression of mammary tumors in nude mice created from green fluorescent protein-tagged MDA-MB-435 bone metastatic variant. Fluorescence image analysis of primary tumor growth demonstrated a statistically significant decrease in tumor area by dietary grape polyphenols. Molecular analysis of excised tumors demonstrated that reduced mammary tumor growth may be due to upregulation of FOXO1 (forkhead box O1) and NFKBIA (IkappaBalpha), thus activating apoptosis and potentially inhibiting NfkappaB (nuclear factor kappaB) activity. Image analysis of distant organs for metastases demonstrated that grape polyphenols reduced metastasis especially to liver and bone. Overall, these results indicate that combined dietary grape polyphenols are effective at inhibition of mammary tumor growth and site-specific metastasis.

  19. Hematopoietic colony-stimulating factors mediate tumor-nerve interactions and bone cancer pain

    NARCIS (Netherlands)

    Schweizerhof, Matthias; Stösser, Sebastian; Kurejova, Martina; Njoo, Christian; Gangadharan, Vijayan; Agarwal, Nitin; Schmelz, Martin; Bali, Kiran Kumar; Michalski, Christoph W.; Brugger, Stefan; Dickenson, Anthony; Simone, Donald A.; Kuner, Rohini

    2009-01-01

    Pain is one of the most severe and debilitating symptoms associated with several forms of cancer. Various types of carcinomas and sarcomas metastasize to skeletal bones and cause spontaneous bone pain and hyperalgesia, which is accompanied by bone degradation and remodeling of peripheral nerves.

  20. Validation of International Classification of Diseases coding for bone metastases in electronic health records using technology-enabled abstraction

    Directory of Open Access Journals (Sweden)

    Liede A

    2015-11-01

    Full Text Available Alexander Liede,1 Rohini K Hernandez,1 Maayan Roth,2 Geoffrey Calkins,2 Katherine Larrabee,2 Leo Nicacio21Center for Observational Research, Amgen Inc., South San Francisco and Thousand Oaks, CA, 2Flatiron Health, New York, NY, USAObjective: The accuracy of bone metastases diagnostic coding based on International Classification of Diseases, ninth revision (ICD-9 is unknown for most large databases used for epidemiologic research in the US. Electronic health records (EHR are the preferred source of data, but often clinically relevant data occur only as unstructured free text. We examined the validity of bone metastases ICD-9 coding in structured EHR and administrative claims relative to the complete (structured and unstructured patient chart obtained through technology-enabled chart abstraction.Patients and methods: Female patients with breast cancer with ≥1 visit after November 2010 were identified from three community oncology practices in the US. We calculated sensitivity, specificity, positive predictive value (PPV, and negative predictive value (NPV of bone metastases ICD-9 code 198.5. The technology-enabled abstraction displays portions of the chart to clinically trained abstractors for targeted review, thereby maximizing efficiency. We evaluated effects of misclassification of patients developing skeletal complications or treated with bone-targeting agents (BTAs, and timing of BTA.Results: Among 8,796 patients with breast cancer, 524 had confirmed bone metastases using chart abstraction. Sensitivity was 0.67 (95% confidence interval [CI] =0.63–0.71 based on structured EHR, and specificity was high at 0.98 (95% CI =0.98–0.99 with corresponding PPV of 0.71 (95% CI =0.67–0.75 and NPV of 0.98 (95% CI =0.98–0.98. From claims, sensitivity was 0.78 (95% CI =0.74–0.81, and specificity was 0.98 (95% CI =0.98–0.98 with PPV of 0.72 (95% CI =0.68–0.76 and NPV of 0.99 (95% CI =0.98–0.99. Structured data and claims missed 17% of bone

  1. Targeted Therapies for Brain Metastases from Breast Cancer

    Directory of Open Access Journals (Sweden)

    Vyshak Alva Venur

    2016-09-01

    Full Text Available The discovery of various driver pathways and targeted small molecule agents/antibodies have revolutionized the management of metastatic breast cancer. Currently, the major targets of clinical utility in breast cancer include the human epidermal growth factor receptor 2 (HER2 and epidermal growth factor receptor (EGFR, vascular endothelial growth factor (VEGF receptor, mechanistic target of rapamycin (mTOR pathway, and the cyclin-dependent kinase 4/6 (CDK-4/6 pathway. Brain metastasis, however, remains a thorn in the flesh, leading to morbidity, neuro-cognitive decline, and interruptions in the management of systemic disease. Approximately 20%–30% of patients with metastatic breast cancer develop brain metastases. Surgery, whole brain radiation therapy, and stereotactic radiosurgery are the traditional treatment options for patients with brain metastases. The therapeutic paradigm is changing due to better understanding of the blood brain barrier and the advent of tyrosine kinase inhibitors and monoclonal antibodies. Several of these agents are in clinical practice and several others are in early stage clinical trials. In this article, we will review the common targetable pathways in the management of breast cancer patients with brain metastases, and the current state of the clinical development of drugs against these pathways.

  2. Targeted Therapies for Brain Metastases from Breast Cancer.

    Science.gov (United States)

    Venur, Vyshak Alva; Leone, José Pablo

    2016-09-13

    The discovery of various driver pathways and targeted small molecule agents/antibodies have revolutionized the management of metastatic breast cancer. Currently, the major targets of clinical utility in breast cancer include the human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) receptor, mechanistic target of rapamycin (mTOR) pathway, and the cyclin-dependent kinase 4/6 (CDK-4/6) pathway. Brain metastasis, however, remains a thorn in the flesh, leading to morbidity, neuro-cognitive decline, and interruptions in the management of systemic disease. Approximately 20%-30% of patients with metastatic breast cancer develop brain metastases. Surgery, whole brain radiation therapy, and stereotactic radiosurgery are the traditional treatment options for patients with brain metastases. The therapeutic paradigm is changing due to better understanding of the blood brain barrier and the advent of tyrosine kinase inhibitors and monoclonal antibodies. Several of these agents are in clinical practice and several others are in early stage clinical trials. In this article, we will review the common targetable pathways in the management of breast cancer patients with brain metastases, and the current state of the clinical development of drugs against these pathways.

  3. Clinical management and outcomes in patients with hyperfunctioning distant metastases from differentiated thyroid cancer after total thyroidectomy and radioactive iodine therapy.

    Science.gov (United States)

    Qiu, Zhong-Ling; Shen, Chen-Tian; Luo, Quan-Yong

    2015-02-01

    Hyperfunctioning distant metastasis (HFDM) from differentiated thyroid cancer (DTC) is a rare entity. This study aimed to assess the outcomes of DTC patients presenting with HFDM after total thyroidectomy and radioactive iodine therapy. A total of 5367 DTC patients treated with (131)I after total thyroidectomy were analyzed retrospectively from January 1991 to June 2013. Therapeutic efficacy was evaluated based on changes in serum thyroglobulin (Tg) and anatomical imaging changes in metastatic lesions. The relationships between survival time and several variables were assessed by univariate and multivariate analyses using the Kaplan-Meier method and Cox's proportional hazards model respectively. Thirty-eight patients with HFDM from DTC were diagnosed, including four with hyperthyroidism, four with subclinical hyperthyroidism, and three with subclinical hypothyroidism. The remaining 27 were euthyroid. Of 25 patients with lung metastases, 84% (21/25) showed disappearance or shrinkage of lung nodules; of 24 patients with bone metastases, 66.67% (16/24) exhibited no obvious imaging changes in metastatic bone lesions after (131)I therapy. Serum Tg decreased significantly in 81.58% (31/38) and increased in 18.42% (7/38) after (131)I therapy. The 10-year survival rate of DTC patients with HFDM was 65.79% (25/38). Multivariate analyses identified age at occurrence of distant metastases (<45 years), only lung metastases, and papillary thyroid cancer (PTC; p=0.032, NA, and 0.043) as independent predictors of survival. The response of hyperfunctioning lung metastases to (131)I treatment was better than that of non-hyperfunctioning lung metastases in DTC, while hyperfunctioning bone metastases responded similarly compared to non-hyperfunctioning bone metastases. Patients younger than 45 years at occurrence of distant metastases, those with only lung metastases, and patients with PTC had better prognoses.

  4. A taxonomy of epithelial human cancer and their metastases

    Directory of Open Access Journals (Sweden)

    De Moor Bart

    2009-12-01

    Full Text Available Abstract Background Microarray technology has allowed to molecularly characterize many different cancer sites. This technology has the potential to individualize therapy and to discover new drug targets. However, due to technological differences and issues in standardized sample collection no study has evaluated the molecular profile of epithelial human cancer in a large number of samples and tissues. Additionally, it has not yet been extensively investigated whether metastases resemble their tissue of origin or tissue of destination. Methods We studied the expression profiles of a series of 1566 primary and 178 metastases by unsupervised hierarchical clustering. The clustering profile was subsequently investigated and correlated with clinico-pathological data. Statistical enrichment of clinico-pathological annotations of groups of samples was investigated using Fisher exact test. Gene set enrichment analysis (GSEA and DAVID functional enrichment analysis were used to investigate the molecular pathways. Kaplan-Meier survival analysis and log-rank tests were used to investigate prognostic significance of gene signatures. Results Large clusters corresponding to breast, gastrointestinal, ovarian and kidney primary tissues emerged from the data. Chromophobe renal cell carcinoma clustered together with follicular differentiated thyroid carcinoma, which supports recent morphological descriptions of thyroid follicular carcinoma-like tumors in the kidney and suggests that they represent a subtype of chromophobe carcinoma. We also found an expression signature identifying primary tumors of squamous cell histology in multiple tissues. Next, a subset of ovarian tumors enriched with endometrioid histology clustered together with endometrium tumors, confirming that they share their etiopathogenesis, which strongly differs from serous ovarian tumors. In addition, the clustering of colon and breast tumors correlated with clinico-pathological characteristics

  5. Novel Radiolabeled Bisphosphonates for PET Diagnosis and Endoradiotherapy of Bone Metastases

    OpenAIRE

    Pfannkuchen, Nina; Meckel, Marian; Bergmann, Ralf; Bachmann, Michael; Bal, Chandrasekhar; Sathekge, Mike; Mohnike, Wolfgang; Baum, Richard P; R?sch, Frank

    2017-01-01

    Bone metastases, often a consequence of breast, prostate, and lung carcinomas, are characterized by an increased bone turnover, which can be visualized by positron emission tomography (PET), as well as single-photon emission computed tomography (SPECT). Bisphosphonate complexes of 99mTc are predominantly used as SPECT tracers. In contrast to SPECT, PET offers a higher spatial resolution and, owing to the 68Ge/68Ga generator, an analog to the established 99mTc generator exists. Complexation of...

  6. Improving radionuclide therapy in prostate cancer patients with metastatic bone pain

    NARCIS (Netherlands)

    Lam, M.G.E.H.

    2009-01-01

    Bone seeking radiopharmaceuticals are indicated in cancer patients with multiple painful skeletal metastases. The majority of these patients are hormone-refractory prostate cancer patients in an advanced stage of their disease. Bone seeking radiopharmaceuticals relieve pain and improve the patients

  7. Embolization in combination with radioiodine therapy for bone metastases from differentiated thyroid carcinoma

    NARCIS (Netherlands)

    van Tol, KM; Hew, JM; Jager, PL; Vermey, A; Dullaart, RPF; Links, TP

    BACKGROUND The outcome for patients with bone metastases from differentiated thyroid carcinoma is worse compared to the overall prognosis of patients with differentiated thyroid carcinoma. The aim of this study is to evaluate the effect of embolization with concomitant radioiodine treatment on the

  8. Update of the International Consensus on Palliative Radiotherapy Endpoints for Future Clinical Trials in Bone Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Chow, Edward, E-mail: Edward.Chow@sunnybrook.ca [Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON (Canada); Hoskin, Peter [Mount Vernon Centre for Cancer Treatment, Mount Vernon Hospital, Northwood, Middlesex (United Kingdom); Mitera, Gunita; Zeng Liang [Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON (Canada); Lutz, Stephen [Department of Radiation Oncology, Blanchard Valley Regional Cancer Center, Findlay, OH (United States); Roos, Daniel [Department of Radiation Oncology, Royal Adelaide Hospital, Adelaide, South Australia (Australia); Hahn, Carol [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Linden, Yvette van der [Radiotherapeutic Institute Friesland, Leeuwarden (Netherlands); Hartsell, William [Department of Radiation Oncology, Advocate Good Samaritan Cancer Center, Downers Grove, IL (United States); Kumar, Eshwar [Department of Oncology, Atlantic Health Sciences Cancer Centre, Saint John Regional Hospital, Saint John, NB (Canada)

    2012-04-01

    Purpose: To update the international consensus on palliative radiotherapy endpoints for future clinical trials in bone metastases by surveying international experts regarding previous uncertainties within the 2002 consensus, changes that may be necessary based on practice pattern changes and research findings since that time. Methods and Materials: A two-phase survey was used to determine revisions and new additions to the 2002 consensus. A total of 49 experts from the American Society for Radiation Oncology, the European Society for Therapeutic Radiology and Oncology, the Faculty of Radiation Oncology of the Royal Australian and New Zealand College of Radiologists, and the Canadian Association of Radiation Oncology who are directly involved in the care of patients with bone metastases participated in this survey. Results: Consensus was established in areas involving response definitions, eligibility criteria for future trials, reirradiation, changes in systemic therapy, radiation techniques, parameters at follow-up, and timing of assessments. Conclusion: An outline for trials in bone metastases was updated based on survey and consensus. Investigators leading trials in bone metastases are encouraged to adopt the revised guideline to promote consistent reporting. Areas for future research were identified. It is intended for the consensus to be re-examined in the future on a regular basis.

  9. Advances in Bevacizumab Therapy for Non-small Cell Lung Cancer 
with Brain Metastases

    Directory of Open Access Journals (Sweden)

    Liyan QU

    2016-08-01

    Full Text Available Brain metastases are frequently encountered in patients with non-small cell lung cancer (NSCLC and are a significant cause of morbidity and mortality. Antiangiogenesis therapy plays a major role in the management of brain metastases in lung cancer. Bevacizumab have become the novel method for the treatment of lung cancer with brain metastases beyond the whole brain radiation therapy, stereotactic radiosurgery and chemotherapy. Recently, more and more studies and trials laid emphasis on the bevacizumab for NSCLC with brain metastases treatment. The key point is the efficacy and safety. In this review, bevacizumab therapy of NSCLC with brain metastases were summarized.

  10. Esophageal Cancer with Bone Marrow Hyperplasia Mimicking Bone Metastasis: Report of a Case.

    Science.gov (United States)

    Yasuda, Hiromi; Shimura, Tadanobu; Okigami, Masato; Yoshiyama, Shigeyuki; Ohi, Masaki; Tanaka, Koji; Mohri, Yasuhiko; Kusunoki, Masato

    2016-01-01

    A 63-year-old man visited the clinic with numbness in the right hand. Magnetic resonance imaging demonstrated multiple low-intensity lesions in the cervical vertebrae and sacrum, which was suspicious of cervical bone metastasis. Fluorodeoxyglucose positron emission tomography/computed tomography revealed areas of increased fluorodeoxyglucose uptake in the thoracic esophagus, sternum and sacrum. A flat, elevated esophageal cancer was identified by upper gastrointestinal endoscopy, and the macroscopic appearance indicated early-stage disease. From the cervical, thoracic and abdominal computed tomography images, there were no metastatic lesions except for the bone lesions. To confirm whether the bone lesions were metastatic, we performed bone biopsy. The histopathological diagnosis was bone marrow hyperplasia. It was crucial for treatment planning to establish whether the lesions were distant metastases. Here, we report a case of esophageal cancer with bone marrow hyperplasia mimicking bone metastasis.

  11. Esophageal Cancer with Bone Marrow Hyperplasia Mimicking Bone Metastasis: Report of a Case

    Directory of Open Access Journals (Sweden)

    Hiromi Yasuda

    2016-11-01

    Full Text Available A 63-year-old man visited the clinic with numbness in the right hand. Magnetic resonance imaging demonstrated multiple low-intensity lesions in the cervical vertebrae and sacrum, which was suspicious of cervical bone metastasis. Fluorodeoxyglucose positron emission tomography/computed tomography revealed areas of increased fluorodeoxyglucose uptake in the thoracic esophagus, sternum and sacrum. A flat, elevated esophageal cancer was identified by upper gastrointestinal endoscopy, and the macroscopic appearance indicated early-stage disease. From the cervical, thoracic and abdominal computed tomography images, there were no metastatic lesions except for the bone lesions. To confirm whether the bone lesions were metastatic, we performed bone biopsy. The histopathological diagnosis was bone marrow hyperplasia. It was crucial for treatment planning to establish whether the lesions were distant metastases. Here, we report a case of esophageal cancer with bone marrow hyperplasia mimicking bone metastasis.

  12. Lung cancer brain metastases – the role of neurosurgery

    Directory of Open Access Journals (Sweden)

    V. A. Aleshin

    2016-01-01

    Full Text Available Lung cancer is mostly common occurring oncological disease in the developed countries. Currently lung cancers are subdivided into nonsmall-cell (adenocarcinoma, large-cell, squamous cell and small-cell. The difference in the clinical and morphological picture leads to the necessity of choosing therapeutic approaches to patients of various groups.Lung cancer should be referred to encephalotropic diseases since metastatic lesion of the central nervous system is sufficiently common complication. Successes of complex treatment of primary tumor result in increase of total longlivety currently ther is ageing of patients suffering lung cancer. These factors increase the risk of metastatic lesions of the brain.Interest to the problem of neurosurgical treatment of patients suffering lung cancer is determined by frequency of lesion, varicosity of morphological variants of the disease, requiring various algorithms of treatment and diagnosis.The main role of neurosurgical intervention in cerebral metastases of lung cancer consist in creation of the paled of carrying out combined therapy. Ideally, a neurosurgical operation should be carried out with clearcut observance of oncological principles of ablasty.Adequate comprehensive approach to treatment or patients with cerebral metastases of various forms of lung cancer with the developed of optimal tactics of and stages of treatment would make it possible to increase duration and quality of life of patients.

  13. An allogenic site-specific rat model of bone metastases for nuclear medicine and experimental oncology.

    Science.gov (United States)

    Biesalski, Barbara; Yilmaz, Bengü; Buchholz, Hans-Georg; Bausbacher, Nicole; Schreckenberger, Mathias; Thews, Oliver

    2012-05-01

    Bone metastases are a major problem in several tumor entities affecting the therapeutic decision and the patient's prognosis. Single photon emission computed tomography (SPECT) and positron emission tomography (PET) are promising techniques for identifying bone tumors using gamma- or positron-emitting labeled radiotracers, but the same tracers if labeled with beta-emitters may also be used to apply therapeutic radionuclides for localized irradiation. For the tracer development specifically accumulating in osseous lesions, animal models of bone metastasis are needed. A technique was developed for tumor cell injection into the circulation of the hind limb of rats. For tumor implantation, the arteria epigastrica caudalis superficialis (a branch of the femoral artery) was cannulated, and 2×10(5) cells were injected. By using the allogenic Walker 256 mammary carcinoma cell line, isolated bone metastases were induced. For visualizing of the tumor growth, PET with 18F-fluoride was performed weekly on a μ-PET system. After 2-3 weeks, tumor invasion was confirmed by histology. Three weeks after tumor cell inoculation, PET images showed signs of bone metastases in 9 out of 11 animals. The tumors were located either in the proximal tibia/fibula or in the distal femur. At this time, the animals showed no restrictions in mobility. The tumors grew constantly over time. The final histological analysis showed tumors growing invasively into the bone matrix. With this model, new SPECT or PET tracers can be evaluated for their potency of accumulating in bone metastases in vivo and to determine which are therefore suitable for diagnosis and/or therapy. Copyright © 2012. Published by Elsevier Inc.

  14. The value of a baseline bone scan in patients with newly diagnosed prostate cancer.

    Science.gov (United States)

    Lin, K; Szabo, Z; Chin, B B; Civelek, A C

    1999-08-01

    This study evaluated the role of bone scans in managing newly diagnosed, untreated prostate cancer. Two hundred seventy consecutive staging bone scans in patients (mean age, 69 years) with newly diagnosed prostate cancer who had serum prostate-specific antigen (PSA) determinations and biopsies between January 1995 and October 1997 were evaluated retrospectively. The bone scans were positive for metastatic bone disease in 24 patients and negative in 246. Serum PSA levels, the number of positive biopsy cores, the extent of tumor in the prostate gland, and Gleason scores were all significantly correlated with scintigraphic bone metastases (P bone metastases. Bone metastases were found in 2 of 34 patients with PSA levels of 10.1 to 20 ng/ml, in 3 of 29 patients with PSA values of 20.1 to 50 ng/ml, and in 16 of 30 patients with PSA levels greater than 50.1 ng/ml. Only one patient had a bone metastasis when the prostate cancer involved fewer than 2 biopsy cores (1 of 135) or when disease was confined to one lobe (1 of 131), but the incidence increased significantly when the malignancy involved three or more biopsy cores (20 of 114) or disease was present in both prostate lobes (20 of 118). Four of 160 patients with Gleason scores less than 6 had bone metastases, whereas 20 of 110 patients with Gleason scores greater than 7 had bone metastases. The likelihood of bone metastases is low in patients with newly diagnosed, untreated prostate cancer when the initial PSA level was less than 10 ng/ml, the number of positive biopsy cores was less than 2, tumor was confined to one lobe, or the Gleason score was less than 6. However, none of these criteria can be used to exclude metastatic bone disease. A baseline bone scan is an important staging procedure and should be obtained to provide maximum data for clinical management of the disease.

  15. Drugs Approved for Bone Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for bone cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  16. Influence of sex differences on the progression of cancer-induced bone pain

    DEFF Research Database (Denmark)

    Falk, Sarah; Uldall, Maria Schmidt; Appel, Camilla

    2013-01-01

    Pain caused by bone metastases has a severe impact on the quality of life for many patients with cancer. Good translational in vivo models are required to understand the molecular mechanism and develop better treatment. In the current study we evaluated the influence of sex differences on the pro......Pain caused by bone metastases has a severe impact on the quality of life for many patients with cancer. Good translational in vivo models are required to understand the molecular mechanism and develop better treatment. In the current study we evaluated the influence of sex differences...... on the progression of cancer-induced bone pain....

  17. Diagnosis and Management of Peritoneal Metastases from Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Evgenia Halkia

    2012-01-01

    Full Text Available The management and the outcome of peritoneal metastases or recurrence from epithelial ovarian cancer are presented. The biology and the diagnostic tools of EOC peritoneal metastasis with a comprehensive approach and the most recent literatures data are discussed. The definition and the role of surgery and chemotherapy are presented in order to focuse on the controversial points. Finally, the paper discusses the new data about the introduction of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC in the treatment of advanced epithelial ovarian cancer.

  18. Esophageal Cancer: Associations With (pN+) Lymph Node Metastases.

    Science.gov (United States)

    Rice, Thomas W; Ishwaran, Hemant; Hofstetter, Wayne L; Schipper, Paul H; Kesler, Kenneth A; Law, Simon; Lerut, E M R; Denlinger, Chadrick E; Salo, Jarmo A; Scott, Walter J; Watson, Thomas J; Allen, Mark S; Chen, Long-Qi; Rusch, Valerie W; Cerfolio, Robert J; Luketich, James D; Duranceau, Andre; Darling, Gail E; Pera, Manuel; Apperson-Hansen, Carolyn; Blackstone, Eugene H

    2017-01-01

    To identify the associations of lymph node metastases (pN+), number of positive nodes, and pN subclassification with cancer, treatment, patient, geographic, and institutional variables, and to recommend extent of lymphadenectomy needed to accurately detect pN+ for esophageal cancer. Limited data and traditional analytic techniques have precluded identifying intricate associations of pN+ with other cancer, treatment, and patient characteristics. Data on 5806 esophagectomy patients from the Worldwide Esophageal Cancer Collaboration were analyzed by Random Forest machine learning techniques. pN+, number of positive nodes, and pN subclassification were associated with increasing depth of cancer invasion (pT), increasing cancer length, decreasing cancer differentiation (G), and more regional lymph nodes resected. Lymphadenectomy necessary to accurately detect pN+ is 60 for shorter, well-differentiated cancers (<2.5 cm) and 20 for longer, poorly differentiated ones. In esophageal cancer, pN+, increasing number of positive nodes, and increasing pN classification are associated with deeper invading, longer, and poorly differentiated cancers. Consequently, if the goal of lymphadenectomy is to accurately define pN+ status of such cancers, few nodes need to be removed. Conversely, superficial, shorter, and well-differentiated cancers require a more extensive lymphadenectomy to accurately define pN+ status.

  19. Patterns of distant metastases in vulvar cancer

    NARCIS (Netherlands)

    Prieske, Katharina; Haeringer, Nicole; Grimm, Donata; Trillsch, Fabian; Eulenburg, Christine; Burandt, Eike; Schmalfeldt, Barbara; Mahner, Sven; Mueller, Volkmar; Woelber, Linn

    2016-01-01

    OBJECTIVE: Metastatic vulvar cancer is a rare disease. Information on metastatic patterns and corresponding prognosis or therapeutic approaches is scarce. We therefore analyzed pattern and course of metastatic disease in a large single center cohort. METHODS: All patients with primary squamous-cell

  20. Receptor conversion in distant breast cancer metastases

    NARCIS (Netherlands)

    Hoefnagel, L.D.C.

    2013-01-01

    The routine pathological work-up of breast cancer includes the evaluation of the estrogen receptor (ERα), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) which reveals biological information about the tumour as well as provides predictive biomarkers regarding hormonal

  1. Acupuncture for Cancer-Induced Bone Pain?

    Directory of Open Access Journals (Sweden)

    Carole A. Paley

    2011-01-01

    Full Text Available Bone pain is the most common type of pain in cancer. Bony metastases are common in advanced cancers, particularly in multiple myeloma, breast, prostate or lung cancer. Current pain-relieving strategies include the use of opioid-based analgesia, bisphosphonates and radiotherapy. Although patients experience some pain relief, these interventions may produce unacceptable side-effects which inevitably affect the quality of life. Acupuncture may represent a potentially valuable adjunct to existing strategies for pain relief and it is known to be relatively free of harmful side-effects. Although acupuncture is used in palliative care settings for all types of cancer pain the evidence-base is sparse and inconclusive and there is very little evidence to show its effectiveness in relieving cancer-induced bone pain (CIBP. The aim of this critical review is to consider the known physiological effects of acupuncture and discuss these in the context of the pathophysiology of malignant bone pain. The aim of future research should be to produce an effective protocol for treating CIBP with acupuncture based on a sound, evidence-based rationale. The physiological mechanisms presented in this review suggest that this is a realistic objective.

  2. Breast cancer subtypes and outcomes of central nervous system metastases.

    Science.gov (United States)

    Arslan, Ulku Y; Oksuzoglu, Berna; Aksoy, Sercan; Harputluoglu, Hakan; Turker, Ibrahim; Ozisik, Yavuz; Dizdar, Omer; Altundag, Kadri; Alkis, Necati; Zengin, Nurullah

    2011-12-01

    Central nervous system (CNS) metastases are detected in up to one third of patients with advanced breast cancer, but their incidence and outcomes by breast cancer subtypes are not precisely documented. Herein, we retrospectively analyzed clinicopathologic data of 259 breast cancer patients with CNS metastases to evaluate the association between breast cancer subtypes and CNS metastasis. The patient groups were classified according to their hormone receptor status and HER-2 expression. Median follow-up time among the patients was 42 months and median survival after CNS metastasis detection was 7.8 months. In HER-2 overexpressing group, median time period between the diagnosis of breast cancer and the detection of CNS metastasis (15.9 months) was significantly shorter compared to the other groups (p = 0.01). The triple negative group had the shortest median survival time after CNS metastasis (6.6 months), although statistically not significant (p = 0.3). In multivariate Cox regression analyses, having solitary CNS metastasis (HR 0.4, 95% CI; 0.2-0.7, p = 0.004), and receiving chemotherapy after CNS metastasis (HR 0.4, 95% CI; 0.287-0.772, p = 0.003) were independent prognostic factors for increasing survival after CNS metastasis. In conclusion, new and effective treatment strategies are required for breast carcinoma patients with brain metastasis considering the positive effect of the treatment on survival. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. [Bone metabolism, renal function and immune structure in prostate cancer. Our experience].

    Science.gov (United States)

    Di Francesco, Simona; Tenaglia, Raffaele Lanfranco

    2013-01-01

    Relation studies between bone and immune system converge in recent years in osteoimmunology chapter. It has been suggested that prostate cancer cells may alter bone homeostasis, renal function and the immune system. The aim of this paper is to evaluate bone metabolism, renal function and immune process in prostate cancer patients versus control. Patients with prostate malignancy and bone metastases showed a condition of hypocalcemia and hypophosphatemia associated with increased bone anabolism and lymphopenia, suggesting a possible correlation between bone metabolism and immune context in prostate cancer.

  4. Assessing Response to Radiation Therapy Treatment of Bone Metastases: Short-Term Followup of Radiation Therapy Treatment of Bone Metastases with Diffusion-Weighted Magnetic Resonance Imaging

    Directory of Open Access Journals (Sweden)

    Salvatore Cappabianca

    2014-01-01

    Full Text Available This study examined the usefulness of diffusion-weighted (DW Magnetic Resonance Imaging (MRI in monitoring bone metastases response to radiation therapy in 15 oligometastatic patients. For each metastasis, both mean apparent diffusion coefficient (ADC changes and high b-value DW metastasis/muscle signal intensity ratio (SIR variations were evaluated at 30 ± 5 days and 60 ± 7 days after the end of treatment. On baseline DW-MRI, all bone metastases were hyperintense and had signal intensities higher than normal bone marrow on calculated ADC maps. At follow-up evaluations, 4 patterns of response were identified: (I decreased high b-value DW SIR associated with increased mean ADC (83.3% of cases; (II increased mean ADC with no change of high b-value DW SIR (10% of cases; (III decreased both high b-value DW SIR and mean ADC (3.3% of cases; (IV a reduction in mean ADC associated with an increase in high b-value DW SIR compared to pretreatment values (3.3% of cases. Patterns (I and (II suggested a good response to therapy; pattern (III was classified as indeterminate, while pattern (IV was suggestive of disease progression. This pattern approach may represent a useful tool in the differentiation between treatment-induced necrosis and highly cellular residual tumor.

  5. Pulmonary nodules and metastases in colorectal cancer

    DEFF Research Database (Denmark)

    Nordholm-Carstensen, Andreas

    2016-01-01

    in CRC. In study IV we investigated the significance of mismatch repair status (MMR) for the location of metastatic spread in a nationwide Danish cohort of patients with newly diagnosed CRC between 2010 and 2012. Deficient MMR was associated with a reduced risk of synchronous metastatic disease, however......Patients with newly diagnosed colorectal cancer (CRC) are subjected to a preoperative thoraco-abdominal CT scan to determine the cancer stage. This staging is of relevance with regard to treatment and prognosis. About 20% of the patients have distant metastatic spread at the time of diagnosis, i...... to a SPCM at follow-up, but we found no evidence that IPN should result in intensified diagnostic work-up besides routine follow-up for CRC. Study II was an analysis of the prevalence of and risk factors for SPCM in a Danish nationwide cohort of patients with newly diagnosed CRC from 2001 to 2011. SPCM were...

  6. Traitement chirurgical des metastases sternales du cancer ...

    African Journals Online (AJOL)

    Le carcinome folliculaire est la deuxième tumeur maligne la plus fréquente de la thyroïde et l'invasion hématologique est le moyen de propagation le plus courant de ses métastases. Les localisations secondaires à ces cancers siègent principalement au niveau des poumons, suivi par les localisations osseuses, cérébrales ...

  7. Progress in the Biological Understanding and Management of Breast Cancer-Associated Central Nervous System Metastases

    Science.gov (United States)

    Gonzalez-Angulo, Ana M.

    2013-01-01

    Metastasis to the central nervous system (CNS) is a devastating neurological complication of systemic cancer. Brain metastases from breast cancer have been documented to occur in approximately 10%–16% of cases over the natural course of the disease with leptomeningeal metastases occurring in approximately 2%–5% of cases of breast cancer. CNS metastases among women with breast cancer tend to occur among those who are younger, have larger tumors, and have a more aggressive histological subtype such as the triple negative and HER2-positive subtypes. Treatment of CNS metastases involves various combinations of whole brain radiation therapy, surgery, stereotactic radiosurgery, and chemotherapy. We will discuss the progress made in the treatment and prevention of breast cancer-associated CNS metastases and will delve into the biological underpinnings of CNS metastases including evaluating the role of breast tumor subtype on the incidence, natural history, prognostic outcome, and impact of therapeutic efficacy. PMID:23740934

  8. Endothelial Cells as Precursors for Osteoblasts in the Metastatic Prostate Cancer Bone

    Directory of Open Access Journals (Sweden)

    Ana E. Paiva

    2017-11-01

    Full Text Available Prostate cancer cells metastasize to the bones, causing ectopic bone formation, which results in fractures and pain. The cellular mechanisms underlying new bone production are unknown. In a recent study, Lin and colleagues, by using state-of-the-art techniques, including prostate cancer mouse models in combination with sophisticated in vivo lineage-tracing technologies, revealed that endothelial cells form osteoblasts induced by prostate cancer metastasis in the bone. Strikingly, genetic deletion of osteorix protein from endothelial cells affected prostate cancer–induced osteogenesis in vivo. Deciphering the osteoblasts origin in the bone microenvironment may result in the development of promising new molecular targets for prostate cancer therapy.

  9. [Pulmonary metastases from colon cancer and occult thyroid cancer in the same lobe].

    Science.gov (United States)

    Kozu, Yoshiki; Futagawa, Toshiro; Suzuki, Kenji

    2014-06-01

    A 70-year-old man with a history of surgery for colon cancer was found to have multiple enlarging pulmonary nodules( 2 in the left lower lobe and 1 in the right upper lobe), and was suspected of having pulmonary metastases from colon cancer. He underwent left lower lobectomy, and subsequent histopathological examination revealed that one was a pulmonary metastasis from colon cancer, and the other was a pulmonary metastasis from papillary thyroid cancer. There were no abnormalities in the thyroid gland according to computed tomography and ultrasonography findings. Therefore, the patient was diagnosed with synchronous pulmonary metastases of both colon cancer and occult thyroid cancer in the same lobe. This is an exceedingly rare case;to the best of our knowledge, there has been no report thus far regarding multiple pulmonary metastases from different primary sites.

  10. Breast cancer metastasizing to the stomach mimicking primary gastric cancer: A case report.

    Science.gov (United States)

    Yim, Kwangil; Ro, Sang Mi; Lee, Jieun

    2017-03-28

    Breast cancer with stomach metastasis rare with an incidence of 1% or less among metastatic breast cancer patients. We experienced a case of breast cancer metastasizing to the stomach in 65-year-old female patient. She experienced dyspepsia and poor oral intake before visiting the clinic. Diffuse infiltration with nodular mucosal thickening of the stomach wall was observed, suggesting advanced gastric cancer based on gross endoscopic finding. Spread of poorly cohesive tumor cells in the gastric mucosa observed upon hematoxylin and eosin stain resembled signet ring cell carcinoma, but diffuse positive staining for GATA3 in immunohistochemical stain allowed for a conclusive diagnosis of breast cancer metastasizing to the stomach. Based on the final diagnosis, systemic chemotherapy was administered instead of primary surgical resection. After 2 cycles of docetaxel administration, she showed a partial response based on abdominal computed tomography scan. This case is an unusual presentation of breast cancer metastasizing to the gastrointestinal tract.

  11. CT findings of small bowel metastases from primary lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jae Wook; Ha, Hyun Kwon; Kim, Ah Young; Kim, Gab Choul; Kim, Tae Kyoung; Kim, Pyo Nyun; Lee, Moon Gyu [Ulsan University College of Medicine, Seoul (Korea, Republic of)

    2002-11-01

    To evaluate the CT findings of small bowel metastases from primary lung cancer. Of the 1468 patients with primary lung cancer between 1990 and 2000, 13 patients who had metastasis to the small intestine were collected. Of these 13 patients, nine who underwent CT scan were included for analysis. The pathologic diagnoses of primary lung cancer in these nine patients were squamous cell carcinoma in six, adenocarcinoma in two, and large cell carcinoma in one. CT scans were analyzed with regard to the site and patterns (intraluminal mass/bowel wall thickening/bowel implants) of metastatic masses, and the presence or absence of complication such as intussusception, obstruction, or perforation of the small bowel. The medical records of the patients were also reviewed retrospectively for evaluation of presenting abdominal symptom and time interval of metastases from initial diagnosis of lung cancer. Metastatic lesions were distributed throughout the small intestine: the duodenum in five, the jejunum in four, the ileum in six, and both jejunum and ileum in one patient. The size of metastatic masses of small bowel ranged from 1.3 cm to 5.0 cm (mean size, 2.6 cm) On CT, the small bowel was involved with intraluminal masses (mean size, 3.4 cm) in eight patients, diffuse wall thickening (mean thickness, 1.6 cm) in five, and bowel implants (mean size, 2.2 cm) in two. Complications occurred in seven patients, including intussusceptions without obstruction in two patients and with obstruction in two, obstruction without intussusceptions in two, and bowel perforation in one. Of 9 patients, 6 had at least one symptom referable to the small bowel including abdominal pain in 4, anemia in 3, vomiting in 1, and jaundice in 1. Lung cancer and small bowel lesions were detected simultaneously in four patients and the time interval of metastases from initial diagnosis of lung cancer ranged from 10 days to 30 months (median interval, 54 days) in patients. CT helps in defining the extent and

  12. [Prognostic analysis of patients with liver metastases from colorectal cancer treated with different modes of therapy].

    Science.gov (United States)

    Fang, Hua; Wang, Xing-yuan; Feng, Feng-yi; Wang, Jin-wan

    2010-01-01

    To investigate the potential prognostic factors for patients with liver metastases from colorectal cancer treated with different modes of therapy. The clinicopathological data of 300 patients with liver metastases from colorectal cancers were retrospectively reviewed and analyzed. The median survival of patients with recurrence (MSR) treated with complete and palliative resection of liver metastases and unresectable patients was 48, 19 and 18 months, respectively (P = 0.000). In patients with unresectable liver metastases, systemic chemotherapy plus regional therapy demonstrated a median survival time of 23 months, significantly longer than the 6 months in untreated patients (P = 0.000). Patients who showed response to the first-line therapy demonstrated an improved survival versus the patients who had no response, with a median survival time of 24 vs. 16 months (P = 0.000). Univariate analysis revealed that resection modes of primary diseases and liver metastases, treatment modality for liver metastases, and response to first-line therapy were prognostic factors. Multivariate analysis showed that resection modes of liver metastases, multimodality treatment after liver metastases, and the response to first-line therapy were all independent prognostic factors for patients with liver metastases from colorectal cancer. Resection of liver metastases, multimodality treatment after liver metastases, and response to first-line chemotherapy are all independent prognostic factors for patients with liver metastasis from colorectal cancer.

  13. External beam radiotherapy for palliation of painful bone metastases: pooled data bioeffect dose response analysis of dose fractionation

    Science.gov (United States)

    Naveen, T.; Supe, Sanjay S.; Ganesh, K. M.; Samuel, Jacob

    2009-01-01

    Bone metastases develop in up to 70% of newly diagnosed cancer patients and result in immobility, anxiety, and depression, severely diminishing the patients quality of life. Radiotherapy is a frequently used modality for bone metastasis and has been shown to be effective in reducing metastatic bone pain and in some instances, causing tumor shrinkage or growth inhibition. There is controversy surrounding the optimal fractionation schedule and total dose of external beam radiotherapy, despite many randomized trials and overviews addressing the issue. This study was undertaken to apply BED to clinical fractionation data of radiotherapeutic management of bone metastases in order to arrive at optimum BED values for acceptable level of response rate. A computerised literature search was conducted to identify all prospective clinical studies that addressed the issue of fractionation for the treatment of bone metastasis. The results of these studies were pooled together to form the database for the analysis. A total of 4111 number of patients received radiation dose ranging from 4 to 40.5 Gy in 1 to 15 fractions with dose per fraction ranging from 2 to 10 Gy. Single fraction treatments were delivered in 2013 patients and the dose varied from 4 to 10 Gy. Multifraction treatments were delivered in 2098 patients and the dose varied from 15 to 40.5 Gy. The biological effective dose (BED) was evaluated for each fractionation schedule using the linear quadratic model and an α/β value of 10 Gy. Response rate increased significantly beyond a BED value of 14.4 Gy (p fracture rate of single fraction treatments, minimum BED value of 14.4 Gy is recommended.

  14. Palliative Radiation Therapy in the Management of Brain Metastases, Spinal Cord Compression, and Bone Metastases

    OpenAIRE

    Sejpal, Samir V; Bhate, Amit; Small, William

    2007-01-01

    Radiation therapy plays an important role in both curative and palliative cancer treatment. Palliative radiation therapy is given to alleviate symptoms, restore function, relieve suffering caused by cancer, and improve quality of life. Pain relief, control of bleeding or ulceration, prevention of impending compression or obstruction from tumor, and shrinkage of tumor masses causing symptoms are indications for palliative radiotherapy. Palliative radiotherapy is a very effective tool in allevi...

  15. Evaluation of clinical parameters influencing the development of bone metastasis in breast cancer.

    Science.gov (United States)

    Diessner, Joachim; Wischnewsky, Manfred; Stüber, Tanja; Stein, Roland; Krockenberger, Mathias; Häusler, Sebastian; Janni, Wolfgang; Kreienberg, Rolf; Blettner, Maria; Schwentner, Lukas; Wöckel, Achim; Bartmann, Catharina

    2016-05-12

    The development of metastases is a negative prognostic parameter for the clinical outcome of breast cancer. Bone constitutes the first site of distant metastases for many affected women. The purpose of this retrospective multicentre study was to evaluate if and how different variables such as primary tumour stage, biological and histological subtype, age at primary diagnosis, tumour size, the number of affected lymph nodes as well as grading influence the development of bone-only metastases. This retrospective German multicentre study is based on the BRENDA collective and included 9625 patients with primary breast cancer recruited from 1992 to 2008. In this analysis, we investigated a subgroup of 226 patients with bone-only metastases. Association between bone-only relapse and clinico-pathological risk factors was assessed in multivariate models using the tree-building algorithms "exhausted CHAID (Chi-square Automatic Interaction Detectors)" and CART(Classification and Regression Tree), as well as radial basis function networks (RBF-net), feedforward multilayer perceptron networks (MLP) and logistic regression. Multivariate analysis demonstrated that breast cancer subtypes have the strongest influence on the development of bone-only metastases (χ2 = 28). 29.9 % of patients with luminal A or luminal B (ABC-patients) and 11.4 % with triple negative BC (TNBC) or HER2-overexpressing tumours had bone-only metastases (p bottom line of different mathematical models is the prior importance of subcategories of breast cancer and the age at primary diagnosis for the appearance of osseous metastases. The primary tumour stage, histological subtype, tumour size, the number of affected lymph nodes, grading and NPI seem to have only a minor influence on the development of bone-only metastases.

  16. Multiparametric Magnetic Resonance Imaging of Prostate Cancer Bone Disease: Correlation With Bone Biopsy Histological and Molecular Features.

    Science.gov (United States)

    Perez-Lopez, Raquel; Nava Rodrigues, Daniel; Figueiredo, Ines; Mateo, Joaquin; Collins, David J; Koh, Dow-Mu; de Bono, Johann S; Tunariu, Nina

    2018-02-01

    The aim of this study was to correlate magnetic resonance imaging (MRI) of castration-resistant prostate cancer (CRPC) bone metastases with histological and molecular features of bone metastases. Forty-three bone marrow biopsies from 33 metastatic CRPC (mCRPC) patients with multiparametric MRI and documented bone metastases were evaluated. A second cohort included 10 CRPC patients with no bone metastases. Associations of apparent diffusion coefficient (ADC), normalized b900 diffusion-weighted imaging (nDWI) signal, and signal-weighted fat fraction (swFF) with bone marrow biopsy histological parameters were evaluated using Mann-Whitney U test and Spearman correlations. Univariate and multivariate logistic regression models were analyzed. Median ADC and nDWI signal was significantly higher, and median swFF was significantly lower, in bone metastases than nonmetastatic bone (P < 0.001). In the metastatic cohort, 31 (72.1%) of 43 biopsies had detectable cancer cells. Median ADC and swFF were significantly lower and median nDWI signal was significantly higher in biopsies with tumor cells versus nondetectable tumor cells (898 × 10 mm/s vs 1617 × 10 mm/s; 11.5% vs 62%; 5.3 vs 2.3, respectively; P < 0.001). Tumor cellularity inversely correlated with ADC and swFF, and positively correlated with nDWI signal (P < 0.001). In serial biopsies, taken before and after treatment, changes in multiparametric MRI parameters paralleled histological changes. Multiparametric MRI provides valuable information about mCRPC bone metastases. These data further clinically qualify DWI as a response biomarker in mCRPC.

  17. A Case of Brain Metastases from Breast Cancer Treated with Whole-Brain Radiotherapy and Eribulin Mesylate

    Directory of Open Access Journals (Sweden)

    Carsten Nieder

    2012-01-01

    Full Text Available Patients with triple receptor-negative breast cancer often develop aggressive metastatic disease, which also might involve the brain. In many cases, systemic and local treatment is needed. It is important to consider the toxicity of chemo- and radiotherapy, especially when newly approved drugs become available. Randomised studies leading to drug approval often exclude patients with newly diagnosed brain metastases. Here we report our initial experience with eribulin mesylate and whole-brain radiotherapy (WBRT in a heavily pretreated patient with multiple brain, lung, and bone metastases from triple receptor-negative breast cancer. Eribulin mesylate was given after 4 previous lines for metastatic disease. Two weeks after the initial dose, that is, during the first cycle, the patient was diagnosed with 5 brain metastases with a maximum size of approximately 4.5 cm. She continued chemotherapy and received concomitant WBRT with 10 fractions of 3 Gy. After 3 cycles of eribulin mesylate, treatment was discontinued because of newly diagnosed liver metastases and progression in the lungs. No unexpected acute toxicity was observed. The only relevant adverse reactions were haematological events after the third cycle (haemoglobin 9.5 g/dL, leukocytes 3.1×109/L. The patient died from respiratory failure 18.5 months from diagnosis of metastatic disease, and 2.7 months from diagnosis of brain metastases. To the best of our knowledge, this is the first report on combined WBRT and eribulin mesylate.

  18. Metastases seen on SPECT imaging despite a normal planar bone scan.

    Science.gov (United States)

    Roland, J; van den Weyngaert, D; Krug, B; Brans, B; Scalliet, P; Vandevivere, J

    1995-12-01

    Although bone scintigraphy is an extremely sensitive method for the detection of focal bone disease, small lesions below the resolution of planar imaging may be missed. This is a report of a patient with carcinoma of the breast who showed tumor progression 1 year after initial treatment. Complete evaluation was performed in order to detect the origin of increased level of a tumor marker. Although planar bone scintigraphy could not demonstrate any lesion in the spine, multiple metastases were detected in the lumbar and the thoracic spines on SPECT imaging. Only some of these lesions were seen with MRI. Repeat planar bone imaging 6 weeks later showed multiple bone lesions in the lumbar and thoracic areas.

  19. Tumor-targeting Salmonella typhimurium A1-R prevents experimental human breast cancer bone metastasis in nude mice

    OpenAIRE

    Miwa, Shinji; Yano, Shuya; Zhang, Yong; Matsumoto,Yasunori; Uehara, Fuminari; Yamamoto, Mako; Hiroshima, Yukihiko; Kimura, Hiroaki; Hayashi, Katsuhiro; Yamamoto, Norio; Bouvet, Michael; Tsuchiya, Hiroyuki; Hoffman, Robert M.; Zhao, Ming

    2014-01-01

    Bone metastasis is a lethal and morbid late stage of breast cancer that is currently treatment resistant. More effective mouse models and treatment are necessary. High bone-metastatic variants of human breast cancer cells were selected in nude mice by cardiac injection. After cardiac injection of a high bone-metastatic variant of breast cancer, all untreated mice had bone metastases compared to only 20% with parental cells. Treatment with tumor-targeting Salmonella typhimurium A1-R completely...

  20. Rectal cancer with synchronous liver metastases: Do we have a clear direction?

    Science.gov (United States)

    Pathak, S; Nunes, Q M; Daniels, I R; Smart, N J; Poston, G J; Påhlman, L

    2015-12-01

    Rectal cancer is a common entity and often presents with synchronous liver metastases. There are discrepancies in management guidelines throughout the world regarding the treatment of advanced rectal cancer, which are further compounded when it presents with synchronous liver metastases. The following article examines the evidence regarding treatment options for patients with synchronous rectal liver metastases and suggests potential treatment algorithms. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Occurrence and survival of synchronous pulmonary metastases in colorectal cancer

    DEFF Research Database (Denmark)

    Nordholm-Carstensen, Andreas; Krarup, Peter-Martin; Jorgensen, Lars N

    2014-01-01

    Cancer Group's (DCCG's) database between May 2001 and December 2011. The recorded data were merged with data from the Danish Pathology Registry and the National Patient Registry. Multivariable logistic- and extended Cox regression analyses were used to adjust for confounding variables. RESULTS: In total......, 1970 patients (7.5%) had pulmonary SCCM of whom 736 (37%) had metastases exclusively in the lungs. Advanced age, recent years of diagnosis and a rectal index cancer were significantly associated with pulmonary SCCM. Adjustment for excess use of thoracic CT scans in rectal cancer patients did not alter...... of pulmonary SCCM was higher than previously reported and had a severe impact on survival. Our analyses suggest that pulmonary metastasectomy, resection of the primary tumour and chemotherapy may be a sound strategy in patients with confined pulmonary SCCM, but the risk of selection bias and consequent...

  2. Predicting the risk of bone metastasis in prostate cancer.

    Science.gov (United States)

    Briganti, Alberto; Suardi, Nazareno; Gallina, Andrea; Abdollah, Firas; Novara, Giacomo; Ficarra, Vincenzo; Montorsi, Francesco

    2014-02-01

    The ability to identify prostate cancer patients at 'high risk' for bone metastasis development could allow early selection of those most likely to benefit from interventions to prevent or delay bone metastasis. This review is aimed to identify potential predictors of risk for bone metastasis in newly diagnosed patients and in those who have already received treatment. At diagnosis, established predictors of prostate cancer aggressiveness (e.g. PSA level, clinical stage, Gleason score) can identify patients at risk for bone metastasis. Following treatment of the disease, increasing evidence suggests that absolute PSA levels and other measures of PSA kinetics are useful to aid prediction of bone metastasis risk in patients both with and without a history of ADT. However, which PSA parameter most accurately predicts risk and the cut-off values that should be employed are unclear. Inclusion of PSA parameters to identify a high risk population may be beneficial in whom bone-modifying treatments are being considered. Other novel (but unvalidated) biomarkers that potentially predict the development of bone metastases have been identified, although it is unclear whether they will have value as independent markers or when combined with other parameters (e.g. measures of PSA kinetics). Further prospective studies of PSA kinetics and other predictive markers are, therefore, required to define the optimal criteria for identifying patients at high risk of bone metastases and those who are most likely to benefit from intensive monitoring and therapeutic intervention. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Pheochromocytoma presenting as musculoskeletal pain from bone metastases

    Energy Technology Data Exchange (ETDEWEB)

    Lynn, M.D.; Braunstein, E.M.; Shapiro, B.

    1987-10-01

    Six patients presented with musculoskeletal pain resulting from destructive bone lesions. These patients were ultimately shown to have metastatic pheochromocytoma. None of the cases exhibited typical symptoms of metastatic pheochromocytoma, nor was it suspected at the time of presentation. In three patients, hypertension caused pheochromocytoma to be considered as a diagnosis. The three remaining patients, all of whom had documented hypertension in the past, underwent bone biopsy. Two of these patients became markedly hypertensive in the postoperative period. Malignant pheochromocytoma may present with metastatic skeletal disease in some patients in whom the presence of hypertension as well as a carefully elicited history may suggest the diagnosis. In such patients, the possibility of pheochromocytoma should be taken into account, as biopsy may trigger a hypertensive crisis in patients not under adrenergic blockade.

  4. Inhibition of breast cancer-cell glutamate release with sulfasalazine limits cancer-induced bone pain.

    Science.gov (United States)

    Ungard, Robert G; Seidlitz, Eric P; Singh, Gurmit

    2014-01-01

    Cancer in bone is frequently a result of metastases from distant sites, particularly from the breast, lung, and prostate. Pain is a common and often severe pathological feature of cancers in bone, and is a significant impediment to the maintenance of quality of life of patients living with bone metastases. Cancer cell lines have been demonstrated to release significant amounts of the neurotransmitter and cell-signalling molecule l-glutamate via the system xC(-) cystine/glutamate antiporter. We have developed a novel mouse model of breast cancer bone metastases to investigate the impact of inhibiting cancer cell glutamate transporters on nociceptive behaviour. Immunodeficient mice were inoculated intrafemorally with the human breast adenocarcinoma cell line MDA-MB-231, then treated 14days later via mini-osmotic pumps inserted intraperitoneally with sulfasalazine, (S)-4-carboxyphenylglycine, or vehicle. Both sulfasalazine and (S)-4-carboxyphenylglycine attenuated in vitro cancer cell glutamate release in a dose-dependent manner via the system xC(-) transporter. Animals treated with sulfasalazine displayed reduced nociceptive behaviours and an extended time until the onset of behavioural evidence of pain. Animals treated with a lower dose of (S)-4-carboxyphenylglycine did not display this reduction in nociceptive behaviour. These results suggest that a reduction in glutamate secretion from cancers in bone with the system xC(-) inhibitor sulfasalazine may provide some benefit for treating the often severe and intractable pain associated with bone metastases. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  5. Prognostic factors associated with survival in patients with symptomatic spinal bone metastases: a retrospective cohort study of 1 043 patients

    Science.gov (United States)

    Bollen, Laurens; van der Linden, Yvette M.; Pondaag, Willem; Fiocco, Marta; Pattynama, Bas P.M.; Marijnen, Corrie A.M.; Nelissen, Rob G.H.H.; Peul, Wilco C.; Dijkstra, P.D. Sander

    2014-01-01

    Background Expected survival is a major factor influencing extent of treatment for symptomatic spinal bone metastases (SBM). Predictive models have been developed, but their use can lead to over- or undertreatment.. The study objective was to identify prognostic factors associated with survival in patients with symptomatic SBM and to create a validated risk stratification model. Methods All patients who were treated for symptomatic SBM between 2001 and 2010 were included in this single center retrospective study. Medical records were reviewed for type of primary cancer, performance status, presence of visceral, brain and bone metastases, number and location of spinal metastases, and neurological functioning. Performance status was assessed with the Karnofsky performance score and neurological functioning with the Frankel scale. Analysis was performed using Kaplan-Meier curves, univariate log-rank tests, Cox regression models, and Harrell's C statistic. Results A total of 1 043 patients were studied. The most prevalent tumors were those of breast (n = 299), lung (n = 250), and prostate (n = 215). Median follow-up duration was 6.6 years, and 6 patients were lost to follow-up. Based on the results of the uni- and multivariate analyses, 4 categories were created. Median survival in category A was 31.2 months (95% CI, 25.2–37.3 months), 15.4 months (95% CI, 11.9–18.2 months) for category B, 4.8 months (95% CI, 4.1–5.4 months) for category C, and 1.6 months (95% CI, 1.4–1.9 months) for category D. Harrell's C statistic was calculated after the model was applied to an external dataset, yielding a result of 0.69. Conclusion Assessing patients according to the presented model results in 4 categories with significantly different survival times. PMID:24470544

  6. The "liver-first approach" for patients with locally advanced rectal cancer and synchronous liver metastases.

    NARCIS (Netherlands)

    Verhoef, C.; Pool, A.E. van der; Nuyttens, J.J.; Planting, A.S.; Eggermont, A.M.M.; Wilt, J.H.W. de

    2009-01-01

    PURPOSE: This study was designed to investigate the outcome of "the liver-first" approach in patients with locally advanced rectal cancer and synchronous liver metastases. METHODS: Patients with locally advanced rectal cancer and synchronous liver metastases were primarily treated for their liver

  7. Does increased local bone resorption secondary to breast and prostate cancer result in increased cartilage degradation?

    DEFF Research Database (Denmark)

    Leeming, Diana J; Byrjalsen, Inger; Qvist, Per

    2008-01-01

    BACKGROUND: Breast and prostate cancer patients often develop lesions of locally high bone turnover, when the primary tumor metastasizes to the bone causing an abnormal high bone resorption at this site. The objective of the present study was to determine whether local increased bone turnover...... experiments revealed that osteoclasts released CTXI fragments but not CTXII from bone specimens. The same was observed for cathepsin K. CONCLUSION: Data suggest that an uncoupling between bone resorption and cartilage degradation occurs in breast and lung cancer patient....

  8. Spontaneous bone metastases in a preclinical orthotopic model of invasive lobular carcinoma; the effect of pharmacological targeting TGFβ receptor I kinase.

    Science.gov (United States)

    Buijs, Jeroen T; Matula, Kasia M; Cheung, Henry; Kruithof-de Julio, Marianna; van der Mark, Maaike H; Snoeks, Thomas J; Cohen, Ron; Corver, Willem E; Mohammad, Khalid S; Jonkers, Jos; Guise, Theresa A; van der Pluijm, Gabri

    2015-04-01

    Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) are the most frequently occurring histological subtypes of breast cancer, accounting for 80-90% and 10-15% of the total cases, respectively. At the time of diagnosis and surgical resection of the primary tumour, most patients do not have clinical signs of metastases, but bone micrometastases may already be present. Our aim was to develop a novel preclinical ILC model of spontaneous bone micrometastasis. We used murine invasive lobular breast carcinoma cells (KEP) that were generated by targeted deletion of E-cadherin and p53 in a conditional K14cre;Cdh1((F/F));Trp53((F/F)) mouse model of de novo mammary tumour formation. After surgical resection of the growing orthotopically implanted KEP cells, distant metastases were formed. In contrast to other orthotopic breast cancer models, KEP cells readily formed skeletal metastases with minimal lung involvement. Continuous treatment with SD-208 (60 mg/kg per day), an orally available TGFβ receptor I kinase inhibitor, increased the tumour growth at the primary site and increased the number of distant metastases. Furthermore, when SD-208 treatment was started after surgical resection of the orthotopic tumour, increased bone colonisation was also observed (versus vehicle). Both our in vitro and in vivo data show that SD-208 treatment reduced TGFβ signalling, inhibited apoptosis, and increased proliferation. In conclusion, we have demonstrated that orthotopic implantation of murine ILC cells represent a new breast cancer model of minimal residual disease in vivo, which comprises key steps of the metastatic cascade. The cancer cells are sensitive to the anti-tumour effects of TGFβ. Our in vivo model is ideally suited for functional studies and evaluation of new pharmacological intervention strategies that may target one or more steps along the metastatic cascade of events. © 2014 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on

  9. A case of recurrent giant cell tumor of bone with malignant transformation and benign pulmonary metastases

    Directory of Open Access Journals (Sweden)

    Gray Robert

    2010-09-01

    Full Text Available Abstract Giant cell tumor (GCT of bone is a locally destructive tumor that occurs predominantly in long bones of post-pubertal adolescents and young adults, where it occurs in the epiphysis. The majority are treated by aggressive curettage or resection. Vascular invasion outside the boundary of the tumor can be seen. Metastasis, with identical morphology to the primary tumor, occurs in a few percent of cases, usually to the lung. On occasion GCTs of bone undergo frank malignant transformation to undifferentiated sarcomas. Here we report a case of GCT of bone that at the time of recurrence was found to have undergone malignant transformation. Concurrent metastases were found in the lung, but these were non-transformed GCT.

  10. Targeting Bone Metabolism in Patients with Advanced Prostate Cancer: Current Options and Controversies

    Directory of Open Access Journals (Sweden)

    Tilman Todenhöfer

    2015-01-01

    Full Text Available Maintaining bone health remains a clinical challenge in patients with prostate cancer (PC who are at risk of developing metastatic bone disease and increased bone loss due to hormone ablation therapy. In patients with cancer-treatment induced bone loss (CTIBL, antiresorptive agents have been shown to improve bone mineral density (BMD and to reduce the risk of fractures. For patients with bone metastases, both zoledronic acid and denosumab delay skeletal related events (SREs in the castration resistant stage of disease. Novel agents targeting the Wnt inhibitors dickkopf-1 and sclerostin are currently under investigation for the treatment of osteoporosis and malignant bone disease. New antineoplastic drugs such as abiraterone, enzalutamide, and Radium-223 are capable of further delaying SREs in patients with advanced PC. The benefit of antiresorptive treatment for patients with castration sensitive PC appears to be limited. Recent trials on the use of zoledronic acid for the prevention of bone metastases failed to be successful, whereas denosumab delayed the occurrence of bone metastases by a median of 4.1 months. Currently, the use of antiresorptive drugs to prevent bone metastases still remains a field of controversies and further trials are needed to identify patient subgroups that may profit from early therapy.

  11. Surgical management of bone metastases: quality of evidence and systematic review.

    Science.gov (United States)

    Wood, Thomas J; Racano, Antonella; Yeung, Herman; Farrokhyar, Forough; Ghert, Michelle; Deheshi, Benjamin M

    2014-12-01

    Surgical management of metastatic bone disease (MBD) is typically reserved for lesions with the highest risk of fracture. However, the high risk of perioperative complications associated with surgery may outweigh the benefits of improved pain and/or function. The goal of this study was to (1) assess the quality of current evidence in this domain; (2) confirm that surgical management of metastases to the long bones and pelvis/acetabulum provides pain relief and improved function; and (3) assess perioperative morbidity and mortality rates. We conducted a systematic review of the literature for clinical studies that reported pain relief and function outcomes, as well as perioperative complications and mortality, in patients with MBD to the long bones and/or pelvis/acetabulum treated surgically. Multiple databases were searched up to January 2012. Pooled weighted proportions are reported. Forty-five studies were included in the final analysis, with 807 patients. All included studies were level IV with 'moderate' overall quality of evidence using the Methodological Index for Non-Randomized Studies scale. Pain relief following surgical management of metastases was 93, 91, and 93 % in the humerus, femur, and pelvis/acetabulum, respectively. Maintained or improved function after surgery was seen in 94, 89, and 94 % in the humerus, femur, and pelvis/acetabulum, respectively. Perioperative complications and mortality were 17 and 4 %, respectively. Despite the inherent limitations of the current evidence, a benefit for the surgical management of bone metastases to the long bones and pelvis/acetabulum is evident; however, there is still substantial risk of perioperative morbidity and mortality that should be considered.

  12. International patterns of practice in radiotherapy for bone metastases: A review of the literature

    Directory of Open Access Journals (Sweden)

    Rachel McDonald

    2014-11-01

    Full Text Available Purpose: Radiation therapy is the standard treatment for symptomatic bone metastases. Several randomized control trials and meta-analyses have concluded a similar efficacy in pain relief when comparing single versus multiple fraction regimes. However, there continues to be reluctance to conform to published guidelines that recommend a single treatment for the palliation of painful bone metastases. The purpose of this literature review is to summarize international patterns of practice, and to determine if guidelines recommending single fraction treatment have been implemented in clinical care. Methods: A literature search was conducted in Ovid Medline, Embase, and Cochrane Central. Search words included, ‘bone metastases’, ‘radiation therapy’, ‘radiotherapy’, ‘patterns of practice’, and ‘dose fractionation’. Both prospective and retrospective studies that investigated the prescription of radiotherapy to bone metastases using actual patient databases were included. Articles were excluded if they investigated hypothetical scenarios. Results: Six hundred and thirteen results were generated from the literature search. Twenty-six articles met the inclusion criteria. Of these, 11 were Canadian, 8 were European, 6 were American, and 1 was Australian. The use of single fraction radiotherapy (SFRT ranged from 3% to 75%, but was generally lower in American studies. Choice of fractionation depended on a variety of factors, including patient age, prognosis, site of irradiation, and physician experience. Conclusion: Despite the publication of robust randomized control trials, meta-analyses, and clinical practice guidelines recommending the use of a single treatment to palliate uncomplicated bone metastasis, SFRT is internationally underutilized.

  13. Effectiveness of Reirradiation for Painful Bone Metastases: A Systematic Review and Meta-Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Huisman, Merel, E-mail: m.huisman-7@umcutrecht.nl [Department of Radiology, University Medical Center Utrecht, Utrecht (Netherlands); Bosch, Maurice A.A.J. van den; Wijlemans, Joost W. [Department of Radiology, University Medical Center Utrecht, Utrecht (Netherlands); Vulpen, Marco van [Department of Radiotherapy, University Medical Center Utrecht, Utrecht (Netherlands); Linden, Yvette M. van der [Department of Clinical Oncology, Leiden University Medical Center, Leiden (Netherlands); Verkooijen, Helena M. [Department of Radiology, University Medical Center Utrecht, Utrecht (Netherlands)

    2012-09-01

    Purpose: Reirradiation of painful bone metastases in nonresponders or patients with recurrent pain after initial response is performed in up to 42% of patients initially treated with radiotherapy. Literature on the effect of reirradiation for pain control in those patients is scarce. In this systematic review and meta-analysis, we quantify the effectiveness of reirradiation for achieving pain control in patients with painful bone metastases. Methods and Materials: A free text search was performed to identify eligible studies using the MEDLINE, EMBASE, and the Cochrane Collaboration library electronic databases. After study selection and quality assessment, a pooled estimate was calculated for overall pain response for reirradiation of metastatic bone pain. Results: Our literature search identified 707 titles, of which 10 articles were selected for systematic review and seven entered the meta-analysis. Overall study quality was mediocre. Of the 2,694 patients initially treated for metastatic bone pain, 527 (20%) patients underwent reirradiation. Overall, a pain response after reirradiation was achieved in 58% of patients (pooled overall response rate 0.58, 95% confidence interval = 0.49-0.67). There was a substantial between-study heterogeneity (I{sup 2} = 63.3%, p = 0.01) because of clinical and methodological differences between studies. Conclusions: Reirradiation of painful bone metastases is effective in terms of pain relief for a small majority of patients; approximately 40% of patients do not benefit from reirradiation. Although the validity of results is limited, this meta-analysis provides a comprehensive overview and the most quantitative estimate of reirradiation effectiveness to date.

  14. Palliative radiation therapy for bone metastases: Update of an ASTRO Evidence-Based Guideline.

    Science.gov (United States)

    Lutz, Stephen; Balboni, Tracy; Jones, Joshua; Lo, Simon; Petit, Joshua; Rich, Shayna E; Wong, Rebecca; Hahn, Carol

    The purpose is to provide an update the Bone Metastases Guideline published in 2011 based on evidence complemented by expert opinion. The update will discuss new high-quality literature for the 8 key questions from the original guideline and implications for practice. A systematic PubMed search from the last date included in the original Guideline yielded 414 relevant articles. Ultimately, 20 randomized controlled trials, 32 prospective nonrandomized studies, and 4 meta-analyses/pooled analyses were selected and abstracted into evidence tables. The authors synthesized the evidence and reached consensus on the included recommendations. Available literature continues to support pain relief equivalency between single and multiple fraction regimens for bone metastases. High-quality data confirm single fraction radiation therapy may be delivered to spine lesions with acceptable late toxicity. One prospective, randomized trial confirms both peripheral and spine-based painful metastases can be successfully and safely palliated with retreatment for recurrence pain with adherence to published dosing constraints. Advanced radiation therapy techniques such as stereotactic body radiation therapy lack high-quality data, leading the panel to favor its use on a clinical trial or when results will be collected in a registry. The panel's conclusion remains that surgery, radionuclides, bisphosphonates, and kyphoplasty/vertebroplasty do not obviate the need for external beam radiation therapy. Updated data analysis confirms that radiation therapy provides excellent palliation for painful bone metastases and that retreatment is safe and effective. Although adherence to evidence-based medicine is critical, thorough expert radiation oncology physician judgment and discretion regarding number of fractions and advanced techniques are also essential to optimize outcomes when considering the patient's overall health, life expectancy, comorbidities, tumor biology, anatomy, previous treatment

  15. Bisphosphonates in patients with renal cell carcinoma and bone metastases: a sunitinib global expanded-access trial subanalysis.

    Science.gov (United States)

    Vrdoljak, Eduard; Gore, Martin; Leyman, Sophie; Szczylik, Cezary; Kharkevich, Galina; Schöffski, Patrick; Torday, Laszlo; Mardiak, Josef; Zhang, Ke; Sajben, Peter; Sella, Avishay

    2015-01-01

    To investigate retrospectively the effects of bone metastases and bisphosphonates in sunitinib-treated metastatic renal cell carcinoma patients. Patients in Groups (Gp) 1 and 2, but not Gp3, had bone metastases. Gp2 received bisphosphonates following standard practice. Gp2 had less favorable prognosis than Gp1. Gp3 had fewer metastases and the best prognosis. More serious adverse events occurred in Gp2 versus Gp1. The difference in overall survival between Gp1 and Gp2 was not significant after adjusting for covariates. Significantly shorter overall survival in Gp1 versus Gp3 persisted after adjusting for covariates. Bone metastases may have a negative prognostic impact in metastatic renal cell carcinoma. Bisphosphonates may have delayed early disease progression for prognostically worse sunitinib/bisphosphonate-treated patients.

  16. At the crossroads: EGFR and PTHrP signaling in cancer-mediated diseases of bone.

    Science.gov (United States)

    Foley, John; Nickerson, Nicole; Riese, David J; Hollenhorst, Peter C; Lorch, Gwendolen; Foley, Anne M

    2012-07-01

    The epidermal growth factor receptor is a well-established cancer therapeutic target due to its stimulation of proliferation, motility, and resistance to apoptosis. Recently, additional roles for the receptor have been identified in growth of metastases. Similar to development, metastatic spread requires signaling interactions between epithelial-derived tumor cells and mesenchymal derivatives of the microenvironment. This necessitates reactivation of developmental signaling molecules, including the hypercalcemia factor parathyroid hormone-related protein. This review covers the variations of epidermal growth factor receptor signaling in cancers that produce bone metastases, regulation of parathyroid hormone-related protein, and evidence that the two molecules drive cancer-mediated diseases of bone.

  17. Mismatch repair status and synchronous metastases in colorectal cancer

    DEFF Research Database (Denmark)

    Nordholm-Carstensen, Andreas; Krarup, Peter-Martin; Morton, Dion

    2015-01-01

    logistic- and Cox-regression and proportional excess hazards analyses were used for confounder adjustment and to adjust for the general population mortality. In total, 983 of 6,692 patients (14.7%) had dMMR and 935 (14.0%) had SCCM. dMMR was associated with a decreased risk of SCCM, adjusted Odds Ratio (a......The causality between the metastatic potential, mismatch repair status (MMR) and survival in colorectal cancer (CRC) is complex. This study aimed to investigate the impact of MMR in CRC on the occurrence of synchronous metastases (SCCM) and survival in patients with SCCM on a national basis....... A nationwide cohort study of 6,692 patients diagnosed with CRC between 2010 and 2012 was conducted. Data were prospectively entered into the Danish Colorectal Cancer Group's database and merged with data from the Danish Pathology Registry and the National Patient Registry. Multivariable and multinomial...

  18. 68Ga Prostate-Specific Membrane Antigen Uptake in Renal Cell Cancer Lymph Node Metastases.

    Science.gov (United States)

    Einspieler, Ingo; Tauber, Robert; Maurer, Tobias; Schwaiger, Markus; Eiber, Matthias

    2016-05-01

    Ga prostate-specific membrane antigen (PSMA)-HBED-CC PET/CT in a patient with a history of both prostate cancer (PC) and renal cell cancer (RCC) shows high PSMA expression in the residual right seminal vesicle suggestive of local recurrence of PC as well as suspected PSMA-positive mediastinal, retroperitoneal, and iliac lymph nodes. Regarding the latter, biopsy revealed lymph node metastases from RCC excluding PC metastases. This case exemplarily demonstrates that high PSMA expression in RCC metastases can potentially mimic PC metastases. Thus, for accurate interpretation of imaging results in PC patients with additional primary tumors, knowledge of PSMA expression of non-PC tissue is necessary.

  19. Toward better use of bone scans among men with early-stage prostate cancer

    Science.gov (United States)

    Merdan, Selin; Womble, Paul R.; Miller, David C.; Barnett, Christine; Ye, Zaojun; Linsell, Susan M.; Montie, James E.; Denton, Brian T.

    2016-01-01

    Objective To evaluate the performance of published guidelines compared to current practice for radiographic staging of men with newly-diagnosed prostate cancer. Materials and Methods Using data from the Michigan Urological Surgery Improvement Collaborative (MUSIC) clinical registry, we identified 1,509 men diagnosed with prostate cancer from March 2012 through June 2013. Clinical data included age, prostate-specific antigen (PSA), Gleason score (GS), clinical T-stage, number of biopsy cores and bone scan (BS) results. We then fit a multivariable logistic regression model to examine the association between clinical variables and the occurrence of bone metastases. Because some patients did not undergo BS, we used established methods to correct for verification bias and estimate the diagnostic accuracy of published guidelines. Results Among 416 men who received a BS, 48 (11.5%) had evidence of bone metastases. Patients with bone metastases were older, with higher PSA and GS (all p Guidelines from the American Urology Association (AUA) and the National Comprehensive Cancer Network (NCCN) demonstrated similar performance in detecting bone metastases in our population, with fewer negative studies than the European Association of Urology (EAU) guideline. Applying the AUA recommendations (i.e., image when PSA >20 or GS ≥8) to current clinical practice, we estimate that guidelines would ensure that BS is performed for almost all men with bone metastases, while avoiding many negative imaging studies. PMID:25096341

  20. Radiological Patterns of Brain Metastases in Breast Cancer Patients: A Subproject of the German Brain Metastases in Breast Cancer (BMBC Registry

    Directory of Open Access Journals (Sweden)

    Elena Laakmann

    2016-09-01

    Full Text Available Evidence about distribution patterns of brain metastases with regard to breast cancer subtypes and its influence on the prognosis of patients is insufficient. Clinical data, cranial computed tomography (CT and magnetic resonance imaging (MRI scans of 300 breast cancer patients with brain metastases (BMs were collected retrospectively in four centers participating in the Brain Metastases in Breast Cancer Registry (BMBC in Germany. Patients with positive estrogen (ER, progesterone (PR, or human epidermal growth factor receptor 2 (HER2 statuses, had a significantly lower number of BMs at diagnosis. Concerning the treatment mode, HER2-positive patients treated with trastuzumab before the diagnosis of BMs showed a lower number of intracranial metastases (p < 0.001. Patients with a HER2-positive tumor-subtype developed cerebellar metastases more often compared with HER2-negative patients (59.8% vs. 44.5%, p = 0.021, whereas patients with triple-negative primary tumors had leptomeningeal disease more often (31.4% vs. 18.3%, p = 0.038. The localization of Brain metastases (BMs was associated with prognosis: patients with leptomeningeal disease had shorter survival compared with patients without signs of leptomeningeal disease (median survival 3 vs. 5 months, p = 0.025. A shorter survival could also be observed in the patients with metastases in the occipital lobe (median survival 3 vs. 5 months, p = 0.012. Our findings suggest a different tumor cell homing to different brain regions depending on subtype and treatment.

  1. Pattern of skeletal metastases from breast cancer in an Asian ...

    African Journals Online (AJOL)

    Background: Breast cancer is a disease that is prevalent world wide and frequently metastasis to the bones . ... designed for the collection of patients' data for evaluation, which was then entered on database and analyzed on the Statistical Package for Social Sciences (SPSS). Patient were staged using TNM Classification.

  2. The impact of pulmonary metastasectomy in patients with previously resected colorectal cancer liver metastases.

    Directory of Open Access Journals (Sweden)

    Armin Wiegering

    Full Text Available 40-50% of patients with colorectal cancer (CRC will develop liver metastases (CRLM during the course of the disease. One third of these patients will additionally develop pulmonary metastases.137 consecutive patients with CRLM, were analyzed regarding survival data, clinical, histological data and treatment. Results were stratified according to the occurrence of pulmonary metastases and metastases resection.39% of all patients with liver resection due to CRLM developed additional lung metastases. 44% of these patients underwent subsequent pulmonary resection. Patients undergoing pulmonary metastasectomy showed a significantly better five-year survival compared to patients not qualified for curative resection (5-year survival 71.2% vs. 28.0%; p = 0.001. Interestingly, the 5-year survival of these patients was even superior to all patients with CRLM, who did not develop pulmonary metastases (77.5% vs. 63.5%; p = 0.015. Patients, whose pulmonary metastases were not resected, were more likely to redevelop liver metastases (50.0% vs 78.6%; p = 0.034. However, the rate of distant metastases did not differ between both groups (54.5 vs.53.6; p = 0.945.The occurrence of colorectal lung metastases after curative liver resection does not impact patient survival if pulmonary metastasectomy is feasible. Those patients clearly benefit from repeated resections of the liver and the lung metastases.

  3. Comparison of CE-FDG-PET/CT with CE-FDG-PET/MR in the evaluation of osseous metastases in breast cancer patients

    OpenAIRE

    Catalano, O A; Nicolai, E; Rosen, B R; Luongo, A; Catalano, M; Iannace, C; Guimaraes, A; Vangel, M G; Mahmood, U; Soricelli, A; Salvatore, M

    2015-01-01

    Background: Despite improvements in treatments, metastatic breast cancer remains difficult to cure. Bones constitute the most common site of first-time recurrence, occurring in 40?75% of cases. Therefore, evaluation for possible osseous metastases is crucial. Technetium 99 (99Tc) bone scintigraphy and fluorodexossyglucose (FDG) positron emission tomography (PET)-computed tomography (PET-CT) are the most commonly used techniques to assess osseous metastasis. PET magnetic resonance (PET-MR) ima...

  4. Brain Metastases in Gastrointestinal Cancers: Is there a Role for Surgery?

    Science.gov (United States)

    Lemke, Johannes; Scheele, Jan; Kapapa, Thomas; von Karstedt, Silvia; Wirtz, Christian Rainer; Henne-Bruns, Doris; Kornmann, Marko

    2014-01-01

    About 10% of all cancer patients will develop brain metastases during advanced disease progression. Interestingly, the vast majority of brain metastases occur in only three types of cancer: Melanoma, lung and breast cancer. In this review, we focus on summarizing the prognosis and impact of surgical resection of brain metastases originating from gastrointestinal cancers such as esophageal, gastric, pancreatic and colorectal cancer. The incidence of brain metastases is cancer and cancer. Overall, prognosis of these patients is very poor with a median survival in the range of only months. Interestingly, a substantial number of patients who had received surgical resection of brain metastases showed prolonged survival. However, it should be taken into account that all these studies were not randomized and it is likely that patients selected for surgical treatment presented with other important prognostic factors such as solitary brain metastases and exclusion of extra-cranial disease. Nevertheless, other reports have demonstrated long-term survival of patients upon resection of brain metastases originating from gastrointestinal cancers. Thus, it appears to be justified to consider aggressive surgical approaches for these patients. PMID:25247579

  5. Treatment of distant metastases from follicular cell-derived thyroid cancer.

    Science.gov (United States)

    Schlumberger, Martin; Leboulleux, Sophie

    2015-01-01

    Distant metastases from thyroid cancer of follicular origin are uncommon. Treatment includes levothyroxine administration at suppressive doses, focal treatment modalities with surgery, external radiation therapy and thermal ablation, and radioiodine in patients with uptake of (131)I in their metastases. Two thirds of distant metastases will become refractory to radioiodine at some point, and when there is a significant tumor burden and documented progression on imaging, a treatment with a kinase inhibitor may provide benefits.

  6. Progressive APOBEC3B mRNA expression in distant breast cancer metastases.

    Directory of Open Access Journals (Sweden)

    Anieta M Sieuwerts

    Full Text Available APOBEC3B was recently identified as a gain-of-function enzymatic source of mutagenesis, which may offer novel therapeutic options with molecules that specifically target this enzyme. In primary breast cancer, APOBEC3B mRNA is deregulated in a substantial proportion of cases and its expression is associated with poor prognosis. However, its expression in breast cancer metastases, which are the main causes of breast cancer-related death, remained to be elucidated.RNA was isolated from 55 primary breast cancers and paired metastases, including regional lymph node (N = 20 and distant metastases (N = 35. APOBEC3B mRNA levels were measured by RT-qPCR. Expression levels of the primary tumors and corresponding metastases were compared, including subgroup analysis by estrogen receptor (ER/ESR1 status.Overall, APOBEC3B mRNA levels of distant metastases were significantly higher as compared to the corresponding primary breast tumor (P = 0.0015, an effect that was not seen for loco-regional lymph node metastases (P = 0.23. Subgroup analysis by ER-status showed that increased APOBEC3B levels in distant metastases were restricted to metastases arising from ER-positive primary breast cancers (P = 0.002. However, regarding ER-negative primary tumors, only loco-regional lymph node metastases showed increased APOBEC3B expression when compared to the corresponding primary tumor (P = 0.028.APOBEC3B mRNA levels are significantly higher in breast cancer metastases as compared to the corresponding ER-positive primary tumors. This suggests a potential role for APOBEC3B in luminal breast cancer progression, and consequently, a promising role for anti-APOBEC3B therapies in advanced stages of this frequent form of breast cancer.

  7. Transarterial chemoembolisation (TACE) with gemcitabine: Phase II study in patients with liver metastases of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Eichler, Katrin, E-mail: k.eichler@em.uni-frankfurt.de; Jakobi, Silke; Gruber-Rouh, Tatjana; Hammerstingl, Renate; Vogl, Thomas J.; Zangos, Stephan

    2013-12-01

    Objective: Evaluation of the efficacy and tolerability of transarterial chemoembolization with gemcitabine in patients with inoperable liver metastases of breast cancer. Materials and methods: Open-label, prospective non-randomized single-center study design; patients had previous chemotherapy including anthracyclines and/or taxanes in the metastatic setting, adequate bone marrow reserve, sufficient liver/renal function, no centralnervous system metastases, Karnovsky-performance-status >70%, and life expectancy >12 weeks. Forty-three patients were enrolled (median 58 years, range 48–71). A suspension of gemcitabine 1.200 mg/m{sup 2}, 2–10 ml/m{sup 2} of Lipiodol, and 5 ml of a degradable starch microsphere (Embocept) suspension, were administered intra-arterially up to 3 times with a 4-weaks-interval. Dose-limiting toxicit is defined as grade 4 thrombocytopenia, neutropenia, or nonhematologic toxicity > grade 3. Tumor response was evaluated by magnetic resonance (MRI) and computed tomography (CT) imaging. Results: All patients tolerated the treatment well; with no dose limiting toxicities. Imaging follow-up according to the RECIST-criteria (Response Evaluation Criteria in Solid Tumors) revealed a partial response in 3 patients, stable disease in 16 patients and progression in 22 patients. The progression free survival was 3.3 months. A significant correlation exists only with the factor vascularization: strongly vascularized tumors show a significantly lowered response. Patients with complete or partial response and the main fraction of the stable disease group showed in the MRI and angiography only a moderate vascularization. The resulting estimate of the total survival rate amounts to a median of 10.2 months. Conclusion: Transarterial chemoembolization with gemcitabine is well tolerated and provides an alternative treatment method for patients with liver metastases of breast cancer.

  8. Renal Impairment Hampers Bisphosphonate Treatment in a Quarter of Lung Cancer Patients with Bone Metastasis

    DEFF Research Database (Denmark)

    Fabian, Katalin; Puskás, Rita; Kakuk, Tímea

    2017-01-01

    Renal function impairment in lung cancer patients with bone metastases was investigated, as this can limit the application of bisphosphonates representing the gold standard in the management of such cases. Clinicopathological data of 570 lung cancer patients were retrospectively analysed for chan...

  9. Use of Single- versus Multiple-Fraction Palliative Radiation Therapy for Bone Metastases: Population-Based Analysis of 16,898 Courses in a Canadian Province

    Energy Technology Data Exchange (ETDEWEB)

    Olson, Robert A., E-mail: rolson2@bccancer.bc.ca [BC Cancer Agency Centre for the North, Prince George, British Columbia (Canada); University of Northern British Columbia, Prince George, British Columbia (Canada); University of British Columbia, Vancouver, British Columbia (Canada); Tiwana, Manpreet S. [BC Cancer Agency Centre for the North, Prince George, British Columbia (Canada); University of Northern British Columbia, Prince George, British Columbia (Canada); Barnes, Mark [BC Cancer Agency Centre for the North, Prince George, British Columbia (Canada); Kiraly, Andrew; Beecham, Kwamena [BC Cancer Agency Centre for the North, Prince George, British Columbia (Canada); University of Northern British Columbia, Prince George, British Columbia (Canada); Miller, Stacy [BC Cancer Agency Centre for the North, Prince George, British Columbia (Canada); University of British Columbia, Vancouver, British Columbia (Canada); Hoegler, David [University of British Columbia, Vancouver, British Columbia (Canada); BC Cancer Agency Centre for the Southern Interior, Kelowna, British Columbia (Canada); Olivotto, Ivo [University of British Columbia, Vancouver, British Columbia (Canada); BC Cancer Agency Vancouver Centre, Victoria, British Columbia (Canada)

    2014-08-01

    Purpose: There is abundant evidence that a single fraction (SF) of palliative radiation therapy (RT) for bone metastases is equivalent to more protracted and costly multiple fraction courses. Despite this, there is low utilization of SFRT internationally. We sought to determine the utilization of SFRT in a population-based, publicly funded health care system. Methods and Materials: All consecutive patients with bone metastases treated with RT during 2007 to 2011 in British Columbia (BC) were identified. Associations between utilization of SFRT and patient and provider characteristics were investigated. Results: A total of 16,898 courses of RT were delivered to 8601 patients. SFRT was prescribed 49% of the time. There were positive relationships among SFRT utilization and primary tumor group (P<.001; most commonly in prostate cancer), worse prognosis (P<.001), increasing physician experience (P<.001), site of metastases (P<.001; least for spine metastases), and area of training (P<.001; most commonly for oncologists trained in the United Kingdom). There was wide variation in the prescription of SFRT across 5 regional cancer centers, ranging from 25.5% to 73.4%, which persisted after controlling for other, potentially confounding factors (P<.001). Conclusions: The large variability in SFRT utilization across BC Cancer Agency (BCCA) cancer centers suggests there is a strong cultural effect, where physicians' use of SFRT is influenced by their colleagues' practice. SFRT use in BC was similar to that in other Canadian and western European reports but strikingly higher than in the United States. Further work is needed to standardize SFRT prescribing practices internationally for this common indication for RT, with the potential for huge health system cost savings and substantial improvements in patients' quality of life.

  10. Treatment of painful bone metastases by Quadramet: retrospective study in 77 patients 2-year experience; Traitement des metastases osseuses douloureuses par Quadramet: experience retrospective ches 77 patients sur 2 ans

    Energy Technology Data Exchange (ETDEWEB)

    Klingelschmitt, S.; Boulahdour, H.; Blagosklonov, O.; Rudenko, B.; Aubry, R.; Bidet, A.C.; Bosset, J.F.; Cardot, J.C. [Centre Hospitalier Universitaire, 25 - Besancon (France)

    2002-09-01

    Metabolic radiotherapy offers an alternative therapeutic tactic in patients with painful bone metastases. The efficacy and toxicity of Quadramet were evaluated in 77 patients. All patients received a 37 MBq/kg dose of Quadramet, and 13 patients received the dose twice. Then, the efficacy of treatment was evaluated according to WHO/OMS score, to pain relief and modification of opioid treatment. The WHO/OMS score was not changed or increased in 87.5 % (63172) of patients. The pain relief was observed in 77.8 % (56/72) of patients. The antalgic treatment decreased in 76.4 % (55/72) of patients. In patients with prostatic cancer, pain relief (79.2 % of patients) was more noticeable than in patients with breast cancer (76.9 % of patients). An opposite response was observed in 8.3 % (6/72) of patients. The rate of PSA decreased in 42.8 % (12/28) of patients with prostatic cancer. The only toxicity observed was myelo-toxicity. This toxicity was moderate and recovered by 8 weeks. After the second administration of Quadramet as well as after the first, we observed the pain relief in 76.9 % of patients. The results of our study confirm the efficacy and the safety of Quadramet in early painful bone metastases treatment. This treatment can be repeated without decrease of the efficacy. (authors)

  11. Novel Radiolabeled Bisphosphonates for PET Diagnosis and Endoradiotherapy of Bone Metastases.

    Science.gov (United States)

    Pfannkuchen, Nina; Meckel, Marian; Bergmann, Ralf; Bachmann, Michael; Bal, Chandrasekhar; Sathekge, Mike; Mohnike, Wolfgang; Baum, Richard P; Rösch, Frank

    2017-05-18

    Bone metastases, often a consequence of breast, prostate, and lung carcinomas, are characterized by an increased bone turnover, which can be visualized by positron emission tomography (PET), as well as single-photon emission computed tomography (SPECT). Bisphosphonate complexes of 99mTc are predominantly used as SPECT tracers. In contrast to SPECT, PET offers a higher spatial resolution and, owing to the 68Ge/68Ga generator, an analog to the established 99mTc generator exists. Complexation of Ga(III) requires the use of chelators. Therefore, DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), NOTA (1,4,7-triazacyclododecane-1,4,7-triacetic acid), and their derivatives, are often used. The combination of these macrocyclic chelators and bisphosphonates is currently studied worldwide. The use of DOTA offers the possibility of a therapeutic application by complexing the β-emitter 177Lu. This overview describes the possibility of diagnosing bone metastases using [68Ga]Ga-BPAMD (68Ga-labeled (4-{[bis-(phosphonomethyl))carbamoyl]methyl}-7,10-bis(carboxymethyl)-1,4,7,10-tetraazacyclododec-1-yl)acetic acid) as well as the successful application of [177Lu]Lu-BPAMD for therapy and the development of new diagnostic and therapeutic tools based on this structure. Improvements concerning both the chelator and the bisphosphonate structure are illustrated providing new 68Ga- and 177Lu-labeled bisphosphonates offering improved pharmacological properties.

  12. Radiotherapy for bone metastases - Practice in Norway 1997 - 2007. A national registry-based study

    Energy Technology Data Exchange (ETDEWEB)

    Sande Laugsand, Tonje [European Palliative Care Research Centre (PRC), Faculty of Medicine, Norwegian Univ. of Technology and Science (NTNU), Trondheim (Norway)], e-mail: tonje.laugsand@ntnu.no; Kaasa, Stein; Lund, Jo-Aasmund [European Palliative Care Research Centre (PRC), Faculty of Medicine, Norwegian Univ. of Technology and Science (NTNU), Trondheim (Norway); Cancer Clinic, St. Olavs Hospital, Univ. Hospital of Trondheim, Trondheim (Norway); Romundstad, Paal [Dept. of Public Health, Faculty of Medicine, Norwegian Univ. of Technology and Science (NTNU), Trondheim (Norway); Johannesen, Tom Boerge [Cancer Registry of Norway, Oslo (Norway)

    2013-08-15

    Numerous randomised clinical trials have shown that the efficacy of single fraction radiotherapy for metastatic bone pain corresponds to that of multiple fractions of radiotherapy for the majority of patients. It is not clear to which extent single fraction radiotherapy has been implemented into clinical practice. Material and methods: A Norwegian national registry based study was conducted, including all radiotherapy schedules of 8 Gy x 1 and 3 Gy x 10 delivered to bone metastases in 1997 - 2007. Binomial regression analyses were used to study whether treatment centre, primary diagnosis, anatomical region irradiated, age, sex, and travel distance, were associated with the choice of fractionation. Results: A total of 14 380 radiotherapy episodes were identified. During the period 31% of the treatments were delivered as 8 Gy x 1. The proportion of single fraction treatments increased from 16% in 1997 to 41% in 2007. There were substantial differences in the proportion of single fraction treatments between the treatment centres (range 25 - 54%). These differences persisted after adjustment for sex, age, primary diagnosis, anatomical region, and travel distance. Conclusions: The study demonstrates an under utilisation of single fraction treatment for bone metastases in Norway during the study period.

  13. Reporting and Handling of Indeterminate Bone Scan Results in the Staging of Prostate Cancer

    DEFF Research Database (Denmark)

    Petersen, Lars J; Strandberg, Jesper; Stenholt, Louise

    2018-01-01

    Bone scintigraphy is key in imaging skeletal metastases in newly diagnosed prostate cancer. Unfortunately, a notable proportion of scans are not readily classified as positive or negative but deemed indeterminate. The extent of reporting of indeterminate bone scans and how such scans are handled ...... of prostate cancer was insufficiently reported in clinical trials. In the case of indeterminate scans, most studies provided adequate measures to obtain the final status of the patients.......Bone scintigraphy is key in imaging skeletal metastases in newly diagnosed prostate cancer. Unfortunately, a notable proportion of scans are not readily classified as positive or negative but deemed indeterminate. The extent of reporting of indeterminate bone scans and how such scans are handled...... in clinical trials are not known. A systematic review was conducted using electronic databases up to October 2016. The main outcome of interest was the reporting of indeterminate bone scans, analyses of how such scans were managed, and exploratory analyses of the association of study characteristics...

  14. {sup 18}F-Fluoride PET/CT is highly effective for excluding bone metastases even in patients with equivocal bone scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Bortot, Daniel C.; Amorim, Barbara J.; Oki, Glaucia C.; Santos, Allan O.; Lima, Mariana C.L.; Etchebehere, Elba C.S.C.; Ramos, Celso Dario [State University of Campinas (UNICAMP), Division of Nuclear Medicine, Department of Radiology, Avenue Zeferino Vaz, S/N., PO Box 6149, Campinas (Brazil); Gapski, Sergio B. [Medicina Nuclear Diagnostico e Terapia, Nuclear Medicine Clinic, Campinas (Brazil); Barboza, Marycel F.; Mengatti, Jair [Nuclear and Energy Research Institute (IPEN)-CNEN, Radiopharmacy Directory, Sao Paulo (Brazil)

    2012-11-15

    Bone scintigraphy (BS) has been used extensively for many years for the diagnosis of bone metastases despite its low specificity and significant rate of equivocal lesions. {sup 18}F-Fluoride PET/CT has been proven to have a high sensitivity and specificity in the detection of malignant bone lesions, but its effectiveness in patients with inconclusive lesions on BS is not well documented. This study evaluated the ability of {sup 18}F-fluoride PET/CT to exclude bone metastases in patients with various malignant primary tumours and nonspecific findings on BS. We prospectively studied 42 patients (34-88 years of age, 26 women) with different types of tumour. All patients had BS performed for staging or restaging purposes but with inconclusive findings. All patients underwent {sup 18}F-fluoride PET/CT. All abnormalities identified on BS images were visually compared with their appearance on the PET/CT images. All the 96 inconclusive lesions found on BS images of the 42 patients were identified on PET/CT images. {sup 18}F-Fluoride PET/CT correctly excluded bone metastases in 23 patients (68 lesions). Of 19 patients (28 lesions) classified by PET/CT as having metastases, 3 (5 lesions) were finally classified as free of bone metastases on follow-up. The sensitivity, specificity, and positive and negative predictive values of {sup 18}F-fluoride PET/CT were, respectively, 100 %, 88 %, 84 % and 100 % for the identification of patients with metastases (patient analysis) and 100 %, 82 % and 100 % for the identification of metastatic lesions (lesion analysis). The factors that make BS inconclusive do not affect {sup 18}F-fluoride PET/CT which shows a high sensitivity and negative predictive value for excluding bone metastases even in patients with inconclusive conventional BS. (orig.)

  15. Treatment patterns in patients with prostate cancer and bone metastasis among US community-based urology group practices.

    Science.gov (United States)

    Freedland, Stephen J; Richhariya, Akshara; Wang, Huei; Chung, Karen; Shore, Neal D

    2012-08-01

    To evaluate a cohort of United States-based urology practices for patterns related to screening, diagnosis, and treatment of bone metastases in men with castration-resistant prostate cancer. Chart audits at 15 community-based urology group practices were conducted in the United States. Patient charts were eligible for study inclusion and review if they had documented bone metastasis secondary to castration-resistant prostate cancer. Data abstracted include site and patient demographics, diagnosis patterns, and bone metastases treatment between July 2006 and July 2009. A sample of approximately 10 charts per practice was used, starting with the most recent patient who met eligibility requirements. Eligible patients (n = 147) from 15 practices had a mean (SD) age of 67.8 (9.3) years at prostate cancer diagnosis and 72.5 (8.6) years at diagnosis of bone metastasis. Bone metastasis occurred 31.3 months (median) after cancer diagnosis. Seventy-three percent (n = 108) of patients had multiple bone metastases, and 82% (n = 120) had bone metastases in weight-bearing bones at last follow-up. Intravenous bisphosphonates were administered to 49% (72/147) of patients, with 97% (70/72) receiving zoledronic acid. Among patients with castration-resistant prostate cancer and documented bone metastases, approximately one half received intravenous zoledronic acid. This suggests that the other half of patients with bone metastases from prostate cancer remained undertreated for the prevention of skeletal complications based on National Comprehensive Cancer Network guidelines during the study time period. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Prophylaxis of radiotherapy-induced nausea and vomiting in the palliative treatment of bone metastases.

    Science.gov (United States)

    Dennis, Kristopher; Nguyen, Janet; Presutti, Roseanna; DeAngelis, Carlo; Tsao, May; Danjoux, Cyril; Barnes, Elizabeth; Sahgal, Arjun; Holden, Lori; Jon, Florencia; Wong, Shun; Chow, Edward

    2012-08-01

    To document the incidence and timing of radiotherapy-induced nausea and vomiting (RINV) in the treatment of bone metastases among patients receiving prophylaxis with a 5-HT(3) receptor antagonist. Patients receiving single (SF) or multiple fraction (MF) palliative radiotherapy (RT) of moderate or low emetogenic risk for bone metastases were prescribed prophylactic Ondansetron. The frequency and duration of prophylaxis and the use of rescue antiemetics were left to the discretion of the treating physicians. Patients documented episodes of nausea (N) and vomiting (V) in daily diaries before and during RT, and until 10 days following RT completion. Rates of complete prophylaxis (CP) for N&V, respectively (CP = no event and no rescue medication), were calculated for the acute phase (the period from the start of RT to the first day following RT completion inclusive) and the delayed phase (the second to tenth days following RT completion inclusive). Fifty-nine patients were enrolled, and 32 were evaluable. CP rates were as follows: moderate-risk SF group (n = 16), acute phase (CP for N = 56%, CP for V = 69%) and delayed phase (CP for N = 31%, CP for V = 44%); moderate-risk MF group (n = 7), acute phase (CP for N = 71%, CP for V = 57%) and delayed phase (CP for N = 43%, CP for V = 57%); low-risk SF group (n = 8), acute phase (CP for N = 50%, CP for V = 100%) and delayed phase (CP for N = 43%, CP for V = 57%); and low-risk MF group (n = 1), acute phase (CP for N = 100%, CP for V = 100%) and delayed phase (CP for N = 100%, CP for V = 100%). Despite prophylaxis, RINV was common among patients receiving palliative radiotherapy for bone metastases, especially during the delayed phase.

  17. TENIPOSIDE FOR BRAIN METASTASES OF SMALL-CELL LUNG-CANCER - A PHASE-II STUDY

    NARCIS (Netherlands)

    POSTMUS, PE; SMIT, EF; HAAXMAREICHE, H; VANZANDWIJK, N; ARDIZZONI, A; QUOIX, E; KIRKPATRICK, A; SAHMOUD, T; GIACCONE, G

    Purpose: Here we report the results of a phase II study of teniposide, one of the most active drugs against small-cell lung cancer (SCLC), in patients with brain metastases. Patients and Methods: Patients with SCLC who presented with brain metastases at diagnosis (n = 11) or during follow-up

  18. Ultrasound imaging of flow patterns in liver metastases from colorectal cancer

    DEFF Research Database (Denmark)

    Rafaelsen, Søren Rafael; Solvig, Jan

    2004-01-01

    BACKGROUND: The ability of colour Doppler, power Doppler and echo-enhanced Doppler imaging to detect the blood flow in liver metastases from colorectal cancer was investigated. An evaluation was then made to determine whether the flow pattern could be used as an indication of disease elsewhere....... METHODS: Forty-two patients with hepatic metastases from colorectal cancer were examined, 8 of whom had local recurrence of their colorectal cancer. Seventy-seven liver metastases were evaluated with colour Doppler and power Doppler, and the presence or absence of a Doppler signal in the halo or centre...... detection rate to 98% (P liver...

  19. RANK/RANK-L/OPG in Patients with Bone Metastases Treated with Anticancer Agents and Zoledronic Acid: A Prospective Study

    Directory of Open Access Journals (Sweden)

    Laura Mercatali

    2013-05-01

    Full Text Available Patients with solid cancer frequently develop bone metastases (BM. Zoledronic acid (Zometa®, ZA, routinely used to treat patients with BM, acts on osteoclasts and also has antitumor properties. We aimed to assess the effect of ZA over time in novel bone turnover markers (RANK/receptor activator of nuclear factor-k B ligand (RANK-L/ Osteoprotegerin (OPG and to correlate these with serum N-terminal telopeptide (NTX. The study prospectively evaluated levels of RANK, RANK-L and OPG transcripts by real-time PCR and NTX expression by ELISA in the peripheral blood of 49 consecutive patients with advanced breast, lung or prostate cancer. All patients received the standard ZA schedule and were monitored for 12 months. Median baseline values of RANK, RANK-L and OPG were 78.28 (range 7.34–620.64, 319.06 (21.42–1884.41 and 1.52 (0.10–58.02, respectively. At 12 months, the median RANK-L value had decreased by 22% with respect to the baseline, whereas median OPG levels had increased by about 96%. Consequently, the RANK-L/OPG ratio decreased by 56% from the baseline. Median serum NTX levels decreased over the 12-month period, reaching statistical significance (p < 0.0001. Our results would seem to indicate that ZA modulates RANK, RANK-L and OPG expression, thus decreasing osteoclast activity.

  20. The diagnostic and prognostic value of serum bone Gla protein (osteocalcin) in patients with recurrent breast cancer

    DEFF Research Database (Denmark)

    Kamby, C; Egsmose, C; Söletormos, G

    1993-01-01

    Serum bone Gla protein (S-BGP), a marker of bone metabolism, was measured in 60 patients included in a staging programme for recurrent breast cancer. Other diagnostic procedures comprised S-alkaline phosphatase (S-AP), bone scan (B-scan), bilateral iliac crest bone marrow biopsies, and radiological...... bone survey. The sites of recurrence were bone (61%), bone marrow (46%), soft tissue (52%), lung (13%), pleura (11%), liver (4%), and brain (2%). Radiology and bone biopsy served as key diagnoses as to the presence or absence of bone metastases. The diagnostic efficiency of B-scan and S-AP was greater...

  1. Current challenges in the management of breast cancer brain metastases.

    Science.gov (United States)

    O'Sullivan, Ciara C; Davarpanah, Nicole N; Abraham, Jame; Bates, Susan E

    2017-04-01

    Approximately 50% of patients with advanced human epidermal growth factor 2 (HER2)-positive breast cancer and triple-negative breast cancer (TNBC) ultimately develop breast cancer brain metastases (BCBM), which are associated with significant morbidity and mortality. The advent of HER2-directed therapy resulted in greatly improved survival outcomes, but unfortunately at the price of an increased cumulative incidence of BCBM. We review challenges in the management of BCBM, and potential treatment strategies, including novel agents such as poly-adenosine diphosphate (ADP) ribose polymerase (PARP) inhibitors (olaparib, veliparib), cyclin-dependent kinase 4/6 (CDK4/6) inhibitors (palbociclib, abemaciclib), and taxane derivatives (eg, ANG1005 and TPI-287). The utility of human epidermal growth factor 2 (HER2)-directed therapies-lapatinib, ado-trastuzumab emtansine (T-DM1), neratinib and tucatinib-is also being studied in this setting. We address the need for improved imaging techniques and innovation in clinical trial design. For example, the current practice is to initially administer whole-brain radiotherapy (WBRT) as treatment for patients with multiple BCBM. However, in selected circumstances, first-line systemic treatment may be more appropriate in order to avoid neurocognitive toxicities, and potential options should be evaluated in window of opportunity trials. Other strategies that may aid development of more effective clinical trials and expedite the development of promising agents include the use of different clinical endpoints and different imaging tools. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. [Establish and analyze the predictive model of early stage brain metastases in patients with breast cancer].

    Science.gov (United States)

    Wang, Qiusheng; Wu, Shikai; Sun, Bing; Huang, Zhou; Meng, Xiangying; Huang, Yan

    2015-12-19

    To investigate the risk factors of cerebral metastasis of breast cancer and to provide guidance for the early diagnosis and treatment of brain metastases. Clinical data of postoperative patients with breast cancer were collected in our hospital from 2005 to 2009. All the patients were divided into two groups, with or without brain metastasis. The risk factors of brain metastases of patients with breast cancer were analyzed by the logistic regression. Eight hundred and twenty four early postoperative patients with breast cancer were enrolled. The median follow-up time was 68 months and 199 cases had brain metastasis. The univariate logistic regression results showed that higher grade of tumor, metastases. This model has the predictive value for the occurrence of brain metastases from breast cancer.

  3. Bone scan can be spared in asymptomatic prostate cancer patients with PSA of Gleason score of <=6 at the initial stage of diagnosis.

    Science.gov (United States)

    Tanaka, Nobumichi; Fujimoto, Kiyohide; Shinkai, Takayuki; Nakai, Yasushi; Kuwada, Masaomi; Anai, Satoshi; Miyake, Makito; Hirayama, Akihide; Hasegawa, Masatoshi; Hirao, Yoshihiko

    2011-10-01

    According to several guidelines, it is acceptable to spare a bone scan in the patients who are newly diagnosed with low-risk prostate cancer. Our aim is to clarify a suitable group whereby a bone scan could be spared at the initial staging of prostate cancer. Consecutive 857 patients who were newly diagnosed from 2004 through 2009 and received bone scans using technetium 99m methylene diphosphonate at the initial staging were enrolled. The proportion of positive bone metastases by age distribution, prostate-specific antigen level at diagnosis, Gleason score and clinical T stage were evaluated. Univariate and multivariate logistic regression analyses were performed to identify the predictors of positive bone metastases. Of all 857 patients, 40 patients (4.7%) showed bone metastases. Patients with higher age, prostate-specific antigen level, clinical stage and Gleason score showed significantly higher rate of bone metastases (P Gleason score were independent predictors of bone metastasis. The multivariate analysis showed that both the prostate-specific antigen level >50 ng/ml and the Gleason score ≥4 + 3 were independent predictors of bone metastases. The incidences of bone metastases in patients with a prostate-specific antigen level of ≤20 ng/ml and Gleason score of ≤6 were reasonably low. Collectively, a bone scan is not necessary as a routine examination for these patients at their initial staging of prostate cancer.

  4. Radiological Patterns of Brain Metastases in Breast Cancer Patients : A Subproject of the German Brain Metastases in Breast Cancer (BMBC) Registry

    NARCIS (Netherlands)

    Laakmann, Elena; Witzel, Isabell; Scriba, Verena; Grzyska, Ulrich; zu Eulenburg, Christine; Burchardi, Nicole; Hesse, Tobias; Wuerschmidt, Florian; Fehm, Tanja; Moebus, Volker; von Minckwitz, Gunter; Loibl, Sibylle; Park-Simon, Tjoung-Won; Mueller, Volkmar

    2016-01-01

    Evidence about distribution patterns of brain metastases with regard to breast cancer subtypes and its influence on the prognosis of patients is insufficient. Clinical data, cranial computed tomography (CT) and magnetic resonance imaging (MRI) scans of 300 breast cancer patients with brain

  5. Application of bone scans for prostate cancer staging: Which guideline shows better result?

    Science.gov (United States)

    Chong, Ari; Hwang, Insang; Ha, Jung-min; Yu, Seong Hyeon; Hwang, Eu Chang; Yu, Ho Song; Kim, Sun Ouck; Jung, Seung-Il; Kang, Taek Won; Kwon, Dong Deuk; Park, Kwangsung

    2014-01-01

    Introduction: We evaluated the accuracy of current guidelines by analyzing bone scan results and clinical parameters of patients with prostate cancer to determine the optimal guideline for predicting bone metastasis. Methods: We retrospectively analyzed patients who were diagnosed with prostate cancer and who underwent a bone scan. Bone metastasis was confirmed by bone scan results with clinical and radiological follow-up. Serum prostate-specific antigen, Gleason score, percent of positive biopsy core, clinical staging and bone scan results were analyzed. We analyzed diagnostic performance in predicting bone metastasis of the guidelines of the European Association of Urology (EAU), American Urological Association (AUA), and the National Comprehensive Cancer Network (NCCN) guidelines as well as Briganti’s classification and regression tree (CART). We also compared the percent of positive biopsy core between patients with and without bone metastases. Results: A total 167 of 806 patients had bone metastases. Receiver operating curve analysis revealed that the AUA and EAU guidelines were better for detecting bone metastases than were Briganti’s CART and NCCN. No significant difference was observed between AUA and EAU guidelines. Patients with bone metastases had a higher percent positive core than did patients without metastasis (the cut-off value >55.6). Conclusion: The EAU and AUA guidelines showed better results than did Briganti’s CART and NCCN for predicting bone metastasis in the enrolled patients. A bone scan is strongly recommended for patients who have a higher percent positive core and who meet the EAU and AUA guidelines. PMID:25210554

  6. Remission of Unresectable Lung Metastases from Rectal Cancer After Herbal Medicine Treatment: A Case Report.

    Science.gov (United States)

    Kim, Kyungsuk; Lee, Sanghun

    2016-01-01

    Lung metastasis is frequent in rectal cancer patients and has a poor prognosis, with an expected three-year survival rate of about 10%. Though western medicine has made great strides in the curative resection of liver metastases, resection of lung metastases has lagged far behind. Many preclinical studies have suggested that herbal treatments block metastasis, but few clinical studies have addressed this topic. We present the case of a 57-year-old Asian male with lung metastases from rectal cancer. He first underwent resection of the primary lesion (stage IIA, T3N0M0) and six cycles of adjuvant chemotherapy. Unfortunately, lung metastases were confirmed about one year later. Palliative chemotherapy was begun, but his disease continued to progress after three cycles and chemotherapy was halted. The patient was exclusively treated with herbal medicine-standardized allergen-removed Rhus verniciflua stokes extract combined with Dokhwaljihwang-tang (Sasang constitutional medicine in Korea). After seven weeks of herbal medicine treatment, the lung metastases were markedly improved. Regression of lung metastases has continued; also, the patient's rectal cancer has not returned. He has been receiving herbal medicine for over two years and very few side effects have been observed. We suggest that the herbal regimen used in our patient is a promising candidate for the treatment of lung metastases secondary to rectal cancer, and we hope that this case stimulates further investigation into the efficacy of herbal treatments for metastatic colorectal cancer patients. Copyright © 2016. Published by Elsevier Inc.

  7. International consensus on use of focused ultrasound for painful bone metastases: Current status and future directions.

    Science.gov (United States)

    Huisman, Merel; ter Haar, Gail; Napoli, Alessandro; Hananel, Arik; Ghanouni, Pejman; Lövey, György; Nijenhuis, Robbert J; van den Bosch, Maurice A A J; Rieke, Viola; Majumdar, Sharmila; Marchetti, Luca; Pfeffer, Raphael M; Hurwitz, Mark D

    2015-05-01

    Focused ultrasound surgery (FUS), in particular magnetic resonance guided FUS (MRgFUS), is an emerging non-invasive thermal treatment modality in oncology that has recently proven to be effective for the palliation of metastatic bone pain. A consensus panel of internationally recognised experts in focused ultrasound critically reviewed all available data and developed consensus statements to increase awareness, accelerate the development, acceptance and adoption of FUS as a treatment for painful bone metastases and provide guidance towards broader application in oncology. In this review, evidence-based consensus statements are provided for (1) current treatment goals, (2) current indications, (3) technical considerations, (4) future directions including research priorities, and (5) economic and logistical considerations.

  8. [Liver metastases from colon and rectal cancer in terms of differences in their clinical parameters].

    Science.gov (United States)

    Liška, V; Emingr, M; Skála, M; Pálek, R; Troup, O; Novák, P; Vyčítal, O; Skalický, T; Třeška, V

    2016-02-01

    From the clinical point of view, rectal cancer and colon cancer are clearly different nosological units in their progress and treatment. The aim of this study was to analyse and clarify the differences between the behaviour of liver metastases from colon and rectal cancer. The study of these factors is important for determining an accurate prognosis and indication of the most effective surgical therapy and oncologic treatment of colon and rectal cancer as a systemic disease. 223 patients with metastatic disease of colorectal carcinoma operated at the Department of Surgery, University Hospital in Pilsen between January 1, 2006 and January 31, 2012 were included in our study. The group of patients comprised 145 men (65%) and 117 women (35%). 275 operations were performed. Resection was done in 177 patients and radiofrequency ablation (RFA) in the total of 98 cases. Our sample was divided into 3 categories according to the location of the primary tumor to C (colon), comprising 58 patients, S (c. sigmoideum) in 61 patients, and R (rectum), comprising 101 patients. Significance analysis of the studied factors (age, gender, staging [TNM classification], grading, presence of mucinous carcinoma, type of operation) was performed using ANOVA test. Overall survival (OS), disease-free interval (DFI) or no evidence of disease (NED) were estimated using Kaplan-Meier curves, which were compared with the log-rank and Wilcoxon tests. As regards the comparison of primary origin of colorectal metastases in liver regardless of their treatment (resection and RFA), our study indicated that rectal liver metastases showed a significantly earlier recurrence than colon liver metastases (shorter NED/DFI). Among other factors, a locally advanced finding, further R2 resection of liver metastases and positivity of lymph node metastases were statistically significant for the prognosis of an early recurrence of the primary colon and sigmoid tumor. Furthermore, we proved that in patients with

  9. Extracranial bone metastases from recurrent anaplastic astrocytoma on FDG PET/CT: A case report a care-compliant article.

    Science.gov (United States)

    Li, Zu-Gui; Mu, Hai-Yu

    2017-06-01

    Extracranial bone metastases from astrocytoma are rare and frequently detected as part of multiorgan metastases. It is extremely rare for astrocytoma to have extracranial bone metastases alone. The importance of whole-body fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) imaging in evaluating extracranial metastasis (ECMs) has not been described effectively due to the rarity of this event. The purpose of our case report is to emphasize the role of FDG PET/CT in the assessment of tumor recurrence and extracranial bone metastases from anaplastic astrocytoma. A 25-year-old woman was firstly admitted with a 4-month history of progressive blurred vision, and 2-month history of intermittent headache. Presurgical MRI imaging revealed a large mass in the left trigone of lateral ventricle. Subsequently, she underwent tumor resection, radiotherapy and chemotherapy. A final pathological diagnosis of anaplastic astrocytoma (WHO III) was made. Nearly 12 months after the surgery, the follow-up brain MR imaging revealed a contrast-enhanced lesion in the site of operative region. Whole-body FDG PET/CT imaging was performed to evaluate the situation. Postoperative brain FDG PET/CT showed an abnormal focal FDG uptake corresponding to the contrast-enhanced lesion in the operative area, suggesting a tumor recurrence. Whole-body FDG PET/CT also showed multiple FDG-avid osteosclerotic lesions in the body. It was highly suggestive of extracranial bone metastases. A subsequent open bone biopsy of FDG-avid lesion in right iliac crest was performed. Histopathological and immunohistochemical findings indicated characteristic of glioma. The patient died 1 month later, nearly 13 months after the initial diagnosis. ECMs from anaplastic astrocytoma are extremely rare but they do occur. Whole-body FDG PET/CT imaging with inclusion of brain was valuable in differentiating tumor recurrence from radiation necrosis and in detecting uncommon extracranial bone metastases

  10. Specific genomic aberrations in primary colorectal cancer are associated with liver metastases

    NARCIS (Netherlands)

    Bruin, S.C.; Klijn, C.N.; Liefers, G.J.; Braaf, L.M.; Joosse, S.A.; Van Beers, E.H.; Verwaal, V.J.; Morreau, H.; Wessels, L.F.; Van Velthuysen, M.L.F.; Tollenaar, R.A.E.M.; Van 't Veer, L.J.

    2010-01-01

    Background: Accurate staging of colorectal cancer (CRC) with clinicopathological parameters is important for predicting prognosis and guiding treatment but provides no information about organ site of metastases. Patterns of genomic aberrations in primary colorectal tumors may reveal a chromosomal

  11. Polyclonal breast cancer metastases arise from collective dissemination of keratin 14-expressing tumor cell clusters

    National Research Council Canada - National Science Library

    Kevin J. Cheung; Veena Padmanaban; Vanesa Silvestri; Koen Schipper; Joshua D. Cohen; Amanda N. Fairchild; Michael A. Gorin; James E. Verdone; Kenneth J. Pienta; Joel S. Bader; Andrew J. Ewald

    2016-01-01

    ...? In this study, we used multicolor lineage tracing to demonstrate that polyclonal seeding by cell clusters is a frequent mechanism in a common mouse model of breast cancer, accounting for >90% of metastases...

  12. Headache Caused by Brain Metastases of Castration-resistant Prostate Cancer during Cabazitaxel Therapy.

    Science.gov (United States)

    Watanabe, Keitaro; Kosaka, Takeo; Hongo, Hiroshi; Tamaki, Satoshi; Oya, Mototsugu

    2017-04-07

    We describe the case of a 55-year-old man who underwent four cycles of cabazitaxel therapy for castration-resistant prostate cancer (CRPC). After the fourth cycle of cabazitaxel, the patient experienced severe headaches. Brain gadolinium (Gd) contrast-enhanced magnetic resonance imaging (MRI) revealed multiple brain metastases. A few days later, the patient suffered impaired consciousness that progressed rapidly. The patient was treated for the symptoms of increased intracranial pressure and underwent whole-brain radiation. One month later, the patient's consciousness level and headache had improved. Although brain metastases of prostate cancer are rare, the possibility of brain metastases should be considered for prostate cancer patients, especially when a CRPC patient complains of headache. Additionally, even if major conditions such as cerebral hemorrhage are excluded by the use of non-contrast-enhanced computed tomography, brain Gd contrast-enhanced MRI should be performed in consideration of the possibility of brain metastases of prostate cancer.

  13. The prognostic significance of computerised tomography findings in women with liver metastases from breast cancer.

    Science.gov (United States)

    Mhlanga, J C; Evans, A E; Doyle, S; James, J J; Cornford, E J; Balls, G; Chan, S Y; Ellis, I

    2011-10-01

    While computerised tomography (CT) is used for diagnosis and assessing response to treatment little work has been performed on the prognostic significance of the CT findings in women with liver metastases. The aim of this study was to assess if the CT findings in women diagnosed with liver metastases at the time of first presentation with metastatic breast cancer have any prognostic significance. The staging CT scans of 78 consecutive women diagnosed with liver metastases at the time of first presentation of metastatic breast cancer were reviewed independently by two radiologists who were blinded to survival and the histological features of the tumour. The number and enhancement characteristics of liver metastases, whether metastases were solitary, multiple or diffuse, the diameter of the largest and the sum of the diameter of the five largest lesions, an estimate of % involvement (50%), and the presence of metastases at other sites were assessed. HER-2 and ER status and histological grade of the patient's primary breast cancer were also recorded. Survival was ascertained from hospital records. The prognostic significance of these factors was assessed in a univariate and multivariate fashion. At univariate analysis, number of liver metastases, sum of the diameter of the five largest lesions, percentage estimated involvement, presence of ascites, chest metastases and HER-2 status were significantly associated with reduced survival. Liver metastasis pattern (i.e. whether discrete or multiple), enhancement characteristics, ER status and histological grade were not associated with a significant outcome. At multivariate analysis estimated percentage liver involvement and the presence of chest metastases retained prognostic significance. Estimated percentage involvement was reproducible with 90% concordance between the two observers. The CT appearances of patients with liver metastases at first presentation with metastatic breast cancer provide prognostic information

  14. Intra ovaries thyroid cancer with intraperitoneal, osseous and pulmonary metastases fixing iodine 131; Cancer thyroidien intra-ovarien avec metastases intraperitoneale, osseuse et pulmonaires fixant l'iode 131

    Energy Technology Data Exchange (ETDEWEB)

    Bernard, A.M.; Barge, M.L.; Le Dortz, L.; Herry, J.; Devillers, A. [Centre Eugene-Marquis, Service de medecine nucleaire, 35 - Rennes (France); Vauleon, E.; Kerbrat, P. [Centre Eugene-Marquis, service d' oncologie medicale, 35 - Rennes (France)

    2010-07-01

    Purpose: Intra ovaries localizations of differentiated thyroid cancer are rare. A few metastatic localizations were described. The presented file is this one of bone and lung metastases localizations discovered 14 years after a bilateral ovaries surgery for a mature teratoma with double epidermic and thyroid compound, taking aspect of an ovaries goiter, with changes. Conclusions: In front of the discovery of an ovary goiter, a careful histopathologic examination is necessary, in search of malignant lesions that may be treated by ira-therapy. (N.C.)

  15. When to perform bone scintigraphy in patients with newly diagnosed prostate cancer? a retrospective study.

    Science.gov (United States)

    Lin, Yiwei; Mao, Qiqi; Chen, Bin; Wang, Liujiang; Liu, Ben; Zheng, Xiangyi; Xie, Liping

    2017-06-12

    To determine when a bone scintigraphy investigation is appropriate in patients with newly diagnosed prostate cancer (PCa). We retrospectively reviewed 703 newly diagnosed PCa patients who were referred for bone scintigraphy. The association between age, prostate specific antigen (PSA), Gleason score (GS) and bone scintigraphy result were investigated by series of crude or stratified analysis. Overall, 15.08% (106/703) patients had bone metastases. PSA and GS between positive bone scan group and negative bone scan group were significantly different, while age was not. The incidence of bone metastasis in patient with PSA bone scan. Patients with PSA ≥ 20 ng/ml or GS ≥ 8 were in higher risk of bone metastasis, bone scintigraphy was recommended. But a bone scintigraphy is of limited value in PCa patients with PSA ≤ 20 ng/ml and GS ≤ 7.

  16. Chemotherapy or Liver Transplantation for Nonresectable Liver Metastases From Colorectal Cancer?

    DEFF Research Database (Denmark)

    Dueland, Svein; Guren, Tormod K; Hagness, Morten

    2015-01-01

    OBJECTIVE:: The primary objective was to compare overall survival (OS) in patients with colorectal cancer (CRC) with nonresectable liver-only metastases treated by liver transplantation or chemotherapy. BACKGROUND:: CRC is the third most common cancer worldwide. About 50% of patients will develop....... The reason for the large difference in OS despite similar DFS/PFS is likely different metastatic patterns at relapse/progression. Relapse in the liver transplantation group was often detected as small, slowly growing lung metastases, whereas progression of nonresectable liver metastases was observed...

  17. [Impact of surgery in the management of pancreatic metastases of renal cell cancer].

    Science.gov (United States)

    Bertrand, J; Saint-Aubert, B; Joly, E; Philippe, C; Quenet, F; Carrere, S; Rouanet, P; Domergue, J

    2014-04-01

    Incidence of renal cell carcinoma (RCC) is increasing over the 25 last years. Pancreatic metastases of RCC are rare. The aim of this work was to study overall survival of patients operated for pancreatic metastases of RCC in Montpellier cancer institute. Between 2000 and 2012, a retrospective monocentric study was performed at Montpellier cancer institute. We evaluated the outcomes of curative pancreatic metastases from renal primary and the impact of targeted therapies. Thirty-eight patients were treated in our center for pancreatic metastases of RCC. Twelve patients had a curative surgery of metachronous pancreatic metastases. Four patients were without recurrence after pancreatic resection (33.3%). None had adjuvant therapy. Six patients were treated by targeted therapies, because of metastatic progression. Five of 6 died, the sixth evolved with targeted therapies by thyrosine kinase inhibitor. Average deadline between appearance of metastases and death was 89.9 months for operated patients. Average deadline between appearance of c metastases and death was 33.1 months for the others (P=0.004). Surgical treatment of pancreatic metastases should increase life expectancy of patients. Others studies are necessary to prove the impact of targeted therapies in metastatics patients in this indication. 5. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  18. Efficacy of Magnetic Resonance-guided Focused Ultrasound Surgery for Bone Metastases Pain Palliation

    Science.gov (United States)

    Kawasaki, Motohiro; Nanba, Hirofumi; Kato, Tomonari; Tani, Toshikazu; Ushida, Takahiro

    2011-09-01

    Magnetic resonance-guided focused ultrasound surgery (MRgFUS) is a novel treatment method that achieves non-invasive thermal ablation by focusing many ultrasound waves on a target tissue with real-time monitoring of the location and temperature of the target during the procedure. We investigated the palliative effect on pain and safety of MRgFUS in painful bone metastases. Six patients (mean age, 65.8 years) who met eligibility criteria for the clinical study approved by our Institutional Ethics Committee based on the cooperative protocol were treated with MRgFUS. Targeted sites included the sacrum (n = 1), ilium (n = 2), scapula (n = 2), and femur (n = 1). The mean follow-up period was 9.2 months. All procedures were performed as a single-session treatment using the treatment system that is integrated into the patient table of a magnetic resonance image (MRI) scanner. Endpoints were change in the intensity of pain due to bone metastases from before to after the treatment, as measured on a numerical rating scale, pain interference with daily activities as determined by the Brief pain inventory (BPI), change in images, and safety. Pain relief was obtained in all patients early after treatment, with a reduction in the mean pain score from 6.0±1.3 at baseline to 1.2±1.0 at the end of follow-up as well as in pain interference with daily activities. The mean time required for a single-session treatment was 83.7±37.0 min, with a mean number of sonications required of 13.3±3.7 and mean energy applied of 846.4±273.5 J. No significant growth of tumors was observed, nor were there treatment-related adverse events. These results suggest that MRgFUS has a non-invasive palliative effect on the localized pain in patients with bone metastasis. MRgFUS could become an option in treatment strategies for painful bone metastases in the future.

  19. Metastatic Prostate Cancer and the Bone: Significance and Therapeutic Options.

    Science.gov (United States)

    Gartrell, Benjamin A; Coleman, Robert; Efstathiou, Eleni; Fizazi, Karim; Logothetis, Christopher J; Smith, Matthew R; Sonpavde, Guru; Sartor, Oliver; Saad, Fred

    2015-11-01

    Skeletal involvement is common in metastatic prostate cancer (PCa) and is associated with skeletal-related events (SREs). The interaction of PCa with the bone microenvironment contributes to self-perpetuating progression of cancer in bone. Bone-targeted agents (BTAs) are available for use in metastatic castration-resistant prostate cancer (mCRPC). To review the biology of bone metastases in PCa and to review the clinical trial data for BTAs in PCa. A literature search was conducted in October 2014. Keywords included clinical trial, prostate cancer, denosumab, bisphosphonates, zoledronic acid, radium-223, bone turnover markers, skeletal-related events, and symptomatic skeletal events. The biology of bone metastases in PCa is summarized. Data supporting the use of BTAs in PCa are reviewed, and issues related to the combination and sequencing of available agents are discussed. The osteoclast-targeted agents zoledronic acid and denosumab decrease SREs in mCRPC, and the α-emitting radiopharmaceutical agent radium-223 improves survival and decreases symptomatic skeletal events. Limited data are available to guide the sequence and combination of BTAs with disease-modifying agents, although data support the use of osteoclast-targeted drugs with chemotherapy, androgen-targeted agents, and radium-223. Zoledronic acid does not reduce SREs when started prior to castration resistance, although osteoclast-targeted agents do improve outcomes when used in patients with asymptomatic to minimally symptomatic chemotherapy-naive mCRPC. The optimal sequence of radium-223 with chemotherapy is uncertain, although data suggest the efficacy and tolerability of radium-223 is similar with either sequence. Clinical trials evaluating the combination of BTAs with other agents are under way. The optimization of sequence and combination strategies will guide the best use of available agents. The literature pertaining to bone metastases in prostate cancer (PCa) was reviewed, and the current

  20. Impact of Using Audit Data to Improve the Evidence-Based Use of Single-Fraction Radiation Therapy for Bone Metastases in British Columbia

    Energy Technology Data Exchange (ETDEWEB)

    Olson, Robert A., E-mail: rolson2@bccancer.bc.ca [BC Cancer Agency–Centre for the North, Prince George, British Columbia (Canada); University of Northern British Columbia, Prince George, British Columbia (Canada); University of British Columbia, Vancouver, British Columbia (Canada); Tiwana, Manpreet [BC Cancer Agency–Centre for the North, Prince George, British Columbia (Canada); University of Northern British Columbia, Prince George, British Columbia (Canada); University of British Columbia, Vancouver, British Columbia (Canada); Barnes, Mark [BC Cancer Agency–Centre for the North, Prince George, British Columbia (Canada); Cai, Eric; McGahan, Colleen [BC Cancer Agency Research Centre, Vancouver, British Columbia (Canada); Roden, Kelsey [University of British Columbia, Vancouver, British Columbia (Canada); Yurkowski, Emily [University of Northern British Columbia, Prince George, British Columbia (Canada); Gentles, Quinn [University of British Columbia, Vancouver, British Columbia (Canada); French, John [BC Cancer Agency–Vancouver Centre, Vancouver, British Columbia (Canada); Halperin, Ross [University of British Columbia, Vancouver, British Columbia (Canada); BC Cancer Agency–Centre for the Southern Interior, Kelowna, British Columbia (Canada); Olivotto, Ivo A. [University of Calgary, Calgary, Alberta (Canada); Tom Baker Cancer Centre, Calgary, Alberta (Canada)

    2016-01-01

    Purpose: To assess the impact of a population-based intervention to increase the consistency and use of single-fraction radiation therapy (SFRT) for bone metastases. Methods and Materials: In 2012, an audit of radiation therapy prescriptions for bone metastases in British Columbia identified significant interphysician and -center (26%-73%) variation in the use of SFRT. Anonymous physician-level and identifiable regional cancer center SFRT use data were presented to all radiation oncologists, together with published guidelines, meta-analyses, and recommendations from practice leaders. The use of SFRT for bone metastases from 2007 through 2011 was compared with use of SFRT in 2013, to assess the impact of the audit and educational intervention. Multilevel logistic regression was used to assess the relationship between the usage of SFRT and the timing of the radiation while controlling for potentially confounding variables. Physician and center were included as group effects to account for the clustered structure of the data. Results: A total of 16,898 courses of RT were delivered from 2007 through 2011, and 3200 courses were delivered in 2013. The rates of SFRT use in 2007, 2008, 2009, 2010, 2011, and 2013 were 50.5%, 50.9%, 48.3%, 48.5%, 48.0%, and 59.7%, respectively (P<.001). Use of SFRT increased in each of 5 regional centers: A: 26% to 32%; B: 36% to 56%; C: 39% to 57%; D: 49% to 56%; and E: 73% to 85.0%. Use of SFRT was more consistent; 3 of 5 centers used SFRT for 56% to 57% of bone metastases RT courses. The regression analysis showed strong evidence that the usage of SFRT increased after the 2012 intervention (odds ratio 2.27, 95% confidence interval 2.06-2.50, P<.0001). Conclusion: Assessed on a population basis, an audit-based intervention increased utilization of SFRT for bone metastases. The intervention reversed a trend to decreasing SFRT use, reduced costs, and improved patient convenience. This suggests that dissemination of programmatic quality

  1. Clinical and genetic determinants of ovarian metastases from colorectal cancer.

    Science.gov (United States)

    Ganesh, Karuna; Shah, Ronak H; Vakiani, Efsevia; Nash, Garrett M; Skottowe, Hugh P; Yaeger, Rona; Cercek, Andrea; Lincoln, Anne; Tran, Christina; Segal, Neil H; Reidy, Diane L; Varghese, Anna; Epstein, Andrew S; Sonoda, Yukio; Chi, Dennis; Guillem, Jose; Temple, Larissa; Paty, Philip; Hechtman, Jaclyn; Shia, Jinru; Weiser, Martin; Aguilar, Julio Garcia; Kemeny, Nancy; Berger, Michael F; Saltz, Leonard; Stadler, Zsofia K

    2017-04-01

    Ovarian metastases from colorectal cancer (OM-CRC) often are unresponsive to chemotherapy and are associated with poor survival. To the authors' knowledge, the clinicopathologic and genomic predictors of OM-CRC are poorly characterized and optimal clinical management remains unclear. Women with a histopathological diagnosis of OM-CRC who were treated at Memorial Sloan Kettering Cancer Center from 1999 to 2015 were identified. Next-generation somatic mutation profiling (Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets [MSK-IMPACT]) was performed on 38 OM-CRC cases, including 21 matched tumor pairs/trios. Regression models were used to analyze variables associated with progression-free survival and overall survival (OS). Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS), SMAD family member 4 (SMAD4), and neurotrophic receptor tyrosine kinase 1 (NTRK1) mutations were more frequent in cases of OM-CRC than in instances of CRC occurring without OM. SMAD4 and lysine methyltransferase 2D (KMT2D) mutations were associated with reduced OS. Matched multisite tumor sequencing did not identify OM-specific genomic alterations. Of the 195 patients who underwent oophorectomy for OM-CRC (median age, 49 years with a progression-free survival of 9.4 months and an OS of 23 months from oophorectomy), 76% had extraovarian metastasis (EOM). In multivariable analysis, residual disease after surgery (R2 resection) was associated with worse survival. Patients with EOM were less likely to achieve R0/R1 surgical resection status (complete macroscopic resection without clinical/radiological evidence of disease) (48% vs 94%). However, if R0/R1 resection status was achieved, both patients with (35.9 months vs 12 months) and without (43.2 months vs 14.5 months) EOM were found to have better OS. Among 114 patients with R0/R1 resection status, 23 (20%) had no disease recurrence, including 10 patients (9%) with > 3 years of follow-up. Loss

  2. Combined Microwave Ablation and Cementoplasty in Patients with Painful Bone Metastases at High Risk of Fracture

    Energy Technology Data Exchange (ETDEWEB)

    Pusceddu, Claudio, E-mail: clapusceddu@gmail.com [Regional Referral Center for Oncologic Diseases, Division of Interventional Radiology, Department of Oncological Radiology, Ocological Hospital “A. Businco” (Italy); Sotgia, Barbara, E-mail: barbara.sotgia@gmail.com; Fele, Rosa Maria, E-mail: rosellafele@tiscali.it [Regional Referral Center for Oncological Diseases, Department of Oncological Radiology, Oncological Hospital “A. Businco” (Italy); Ballicu, Nicola, E-mail: nicolaballicu77@gmail.com [Regional Referral Center for Oncologic Diseases, Division of Interventional Radiology, Department of Oncological Radiology, Ocological Hospital “A. Businco” (Italy); Melis, Luca, E-mail: doclucamelis@tiscali.it [Regional Referral Center for Oncological Diseases, Department of Oncological Radiology, Oncological Hospital “A. Businco” (Italy)

    2016-01-15

    PurposeTo retrospectively evaluate the effectiveness of computed tomography-guided percutaneous microwave ablation (MWA) and cementoplasty in patients with painful bone metastases at high risk of fracture.Materials and MethodsThirty-five patients with 37 metastatic bone lesions underwent computed tomography-guided MWA combined with cementoplasty (polymethylmethacrylate injection). Vertebrae, femur, and acetabulum were the intervention sites and the primary end point was pain relief. Pain severity was estimated by visual analog scale (VAS) before treatment; 1 week post-treatment; and 1, 6, and 12 months post-treatment. Functional outcome was assessed by improved patient walking ability. Radiological evaluation was performed at baseline and 3 and 12 months post-procedure.ResultsIn all patients, pain reduction occurred from the first week after treatment. The mean reduction in the VAS score was 84, 90, 90 % at week 1, month 1, and month 6, respectively. Improved walking ability occurred in 100 and 98 % of cases at the 1- and 6-month functional outcome evaluations, respectively. At the 1-year evaluation, 25 patients were alive, and 10 patients (28 %) had died because of widespread disease. The mean reduction in the VAS score and improvement in surviving patients’ walking ability were 90 and 100 %, respectively. No patients showed evidence of local tumor recurrence or progression and pathological fracture in the treated sites.ConclusionOur results suggest that MWA combined with osteoplasty is safe and effective when treating painful bone metastases at high risk of fracture. The number of surviving patients at the 1-year evaluation confirms the need for an effective and long-lasting treatment.

  3. Results of laparoscopic pelvic lymphadenectomy in patients at high risk for nodal metastases from prostate cancer.

    Science.gov (United States)

    Kava, B R; Dalbagni, G; Conlon, K C; Russo, P

    1998-03-01

    Laparoscopic pelvic lymphadenectomy (LPLND) can be performed safely and with minimal morbidity in the staging of prostate cancer. Its utility in evaluating patients at high risk for metastatic disease before primarily nonsurgical treatment modalities was evaluated. Twenty-four consecutive patients who underwent LPLND between June 1993 and July 1996 were studied. These patients were considered poor surgical candidates based on several risk factors, as follows: elevation of serum PSA >20 in 19 patients (79%); elevation of serum acid phosphatase in 4 patients (17%); digital rectal examination findings indicative of extraprostatic extension or seminal vesical involvement in 14 patients (58%); and poorly differentiated tumors on prostate biopsy in 19 patients (79%). Nineteen patients (79%) had two or more of these risk factors. Median PSA for the entire series of patients was 35.2 ng/mL (range 7.9 to 133 ng/mL), and median Gleason score was 7 (range 5 to 9). Preoperative CT or MRI was negative for pelvic lymph node metastases in 17 of 23 patients (79%), and bone scan was negative in all 24 patients. Unilateral (n = 2) or bilateral (n = 22) LPLND was performed in all patients. Six patients (25%) had lymph node metastases detected laparoscopically. Five of the six patients had palpable extraprostatic extension (T3a/b) or invasion of a seminal vesical (T3c), and in four of these patients the site of the metastatic lymph nodes was ipsilateral to the palpable prostate abnormality. None of the risk factors was independently predictive of lymph node metastases within this series of patients. An average of 10.8 +/- 6.5 lymph nodes was removed at a mean operative time of 174 +/- 10 minutes for patients undergoing bilateral LPLND. Estimated blood loss was minimal for 20 of 22 patients (92%) undergoing LPLND alone, and there were no complications requiring open exploration. Mean postoperative hospital stay was 1.2 +/- 0.5 days for patients undergoing LPLND alone. LPLND can be used

  4. [Ovarian metastases of digestive cancers. Diagnostic and therapeutic management].

    Science.gov (United States)

    Lorimier, G; Reigner, B; Rive, C; Cronier, P; Talha, A; Guntz, M

    1988-12-01

    Although ovarian metastasis of digestive cancers were well known since more 80 years, the management of ovaries is still discussed. The authors reviewed 112 cases of digestive tumors in female patients operated between 1973 and 1987, excluding the peritoneal carcinomatosis, and report 7 cases of ovarian metastasis. The primary carcinoma was gastric (2 cases) colonic (2 cases) appendicular (1 case) small bowel (1 case) and biliary tract (1 case). Because the severe prognosis and the frequent revealing and isolated feature of the ovarian metastases the authors review the literature in order to propose recommendations regarding the diagnosis and treatment according to the localisation, the grading of the primary tumor particularly in non menopausal patients. When the primary tumor is a mucinous signet-ring carcinoma with spread to the serosa and a gross abnormality of an ovary is discovered the oophorectomy should be performed. In every cases an immediate histological examination is absolutely necessary. Clinical and sonographic findings are included in the operative staging and the follow up of patients operated for a digestive adenocarcinoma. Especially if the ovarian tumor is bilateral a complete digestive check-up including appendix and biliary tract is necessary.

  5. Molecular and Functional Imaging for Detection of Lymph Node Metastases in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Ansje Fortuin

    2013-07-01

    Full Text Available Knowledge on lymph node metastases is crucial for the prognosis and treatment of prostate cancer patients. Conventional anatomic imaging often fails to differentiate benign from metastatic lymph nodes. Pelvic lymph node dissection is an invasive technique and underestimates the extent of lymph node metastases. Therefore, there is a need for more accurate non-invasive diagnostic techniques. Molecular and functional imaging has been subject of research for the last decades, in this respect. Therefore, in this article the value of imaging techniques to detect lymph node metastases is reviewed. These techniques include scintigraphy, sentinel node imaging, positron emission tomography/computed tomography (PET/CT, diffusion weighted magnetic resonance imaging (DWI MRI and magnetic resonance lymphography (MRL. Knowledge on pathway and size of lymph node metastases has increased with molecular and functional imaging. Furthermore, improved detection and localization of lymph node metastases will enable (focal treatment of the positive nodes only.

  6. Assessment of National Practice for Palliative Radiation Therapy for Bone Metastases Suggests Marked Underutilization of Single-Fraction Regimens in the United States

    Energy Technology Data Exchange (ETDEWEB)

    Rutter, Charles E., E-mail: charles.rutter@yale.edu [Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut (United States); Yale Cancer Center, New Haven, Connecticut (United States); Yu, James B.; Wilson, Lynn D.; Park, Henry S. [Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut (United States); Yale Cancer Center, New Haven, Connecticut (United States)

    2015-03-01

    Purpose: To characterize temporal trends in the application of various bone metastasis fractionations within the United States during the past decade, using the National Cancer Data Base; the primary aim was to determine whether clinical practice in the United States has changed over time to reflect the published randomized evidence and the growing movement for value-based treatment decisions. Patients and Methods: The National Cancer Data Base was used to identify patients treated to osseous metastases from breast, prostate, and lung cancer. Utilization of single-fraction versus multiple-fraction radiation therapy was compared according to demographic, disease-related, and health care system details. Results: We included 24,992 patients treated during the period 2005-2011 for bone metastases. Among patients treated to non-spinal/vertebral sites (n=9011), 4.7% received 8 Gy in 1 fraction, whereas 95.3% received multiple-fraction treatment. Over time the proportion of patients receiving a single fraction of 8 Gy increased (from 3.4% in 2005 to 7.5% in 2011). Numerous independent predictors of single-fraction treatment were identified, including older age, farther travel distance for treatment, academic treatment facility, and non-private health insurance (P<.05). Conclusions: Single-fraction palliative radiation therapy regimens are significantly underutilized in current practice in the United States. Further efforts are needed to address this issue, such that evidence-based and cost-conscious care becomes more commonplace.

  7. Opposite prognostic roles of HIF1β and HIF2β expressions in bone metastatic clear cell renal cell cancer

    DEFF Research Database (Denmark)

    Szendroi, Attila; Szász, A. Marcell; Kardos, Magdolna

    2016-01-01

    BACKGROUND: Prognostic markers of bone metastatic clear cell renal cell cancer (ccRCC) are poorly established. We tested prognostic value of HIF1β/HIF2β and their selected target genes in primary tumors and corresponding bone metastases. RESULTS: Expression of HIF2β was lower in mRCC both at mRNA...

  8. The Src family kinase inhibitor dasatinib delays pain-related behaviour and conserves bone in a rat model of cancer-induced bone pain

    DEFF Research Database (Denmark)

    Appel, Camilla Kristine; Gallego-Pedersen, Simone; Andersen, Line

    2017-01-01

    .o.) from day 7 after inoculation of MRMT-1 mammary carcinoma cells significantly attenuated movement-evoked and non-evoked pain behaviour in cancer-bearing rats. Radiographic - and microcomputed tomographic analyses showed significantly higher relative bone density and considerably preserved bone micro...... subunit 2B. These findings support a role of dasatinib as a disease modifying drug in pain pathologies characterized by increased osteoclast activity, such as bone metastases....

  9. Putting on the Brakes: Blocking the Growth of Metastases | Center for Cancer Research

    Science.gov (United States)

    Most of the suffering and death caused by cancer is due, not to the primary tumor, but to the ability of cancer cells to spread throughout the body and to form metastases in other organs. Breast and prostate cancers often have periods of dormancy, which can extend up to 30 years, between the identification and treatment of a primary tumor and the growth of overt metastases. What induces or inhibits metastatic dormancy is unknown, but prolonging this period may improve the survival of patients with these types of cancer.

  10. Animal Models of Bone Metastasis

    Science.gov (United States)

    Simmons, J. K.; Hildreth, B. E.; Supsavhad, W.; Elshafae, S. M.; Hassan, B. B.; Dirksen, W. P.; Toribio, R. E.; Rosol, T. J.

    2015-01-01

    Bone is one of the most common sites of cancer metastasis in humans and is a significant source of morbidity and mortality. Bone metastases are considered incurable and result in pain, pathologic fracture, and decreased quality of life. Animal models of skeletal metastases are essential to improve the understanding of the molecular pathways of cancer metastasis and growth in bone and to develop new therapies to inhibit and prevent bone metastases. The ideal animal model should be clinically relevant, reproducible, and representative of human disease. Currently, an ideal model does not exist; however, understanding the strengths and weaknesses of the available models will lead to proper study design and successful cancer research. This review provides an overview of the current in vivo animal models used in the study of skeletal metastases or local tumor invasion into bone and focuses on mammary and prostate cancer, lymphoma, multiple myeloma, head and neck squamous cell carcinoma, and miscellaneous tumors that metastasize to bone. PMID:26021553

  11. Dosimetric and clinical impact of 3D vs. 2D planning in palliative radiotherapy for bone metastases.

    Science.gov (United States)

    Pope, Kathy; Fitzpatrick, David; Potter, Andrew; Holwell, Michael; Wang, Lisa; Lau, Michelle; Levin, Wilfred; McLean, Michael; Balaura, Laura Zurawel; Bezjak, Andrea; Wong, Rebecca K S

    2013-08-01

    The incorporation of three-dimensional (3D) planning for the treatment of bone metastases has been embraced in many North American practices with assumed superior tumor targeting, sparing of normal structures, and improvement in patient outcomes. The goal of our project was to evaluate the dosimetric and clinical impact of 3D vs. two-dimensional (2D) planning for patients who require simple palliative radiotherapy techniques (≤ 2 beams) for bone metastases. Patients undergoing palliative radiation therapy for bone metastases were eligible. The study oncologists first documented the intended treatment target, defined the treatment target/field using digital radiographs (2D), followed by using full 3D planning computerized tomography volumetric datasets. Treatment plans were compared dosimetrically, and patient-reported outcomes (pain, fatigue, anorexia, and nausea) were compared against a historical cohort treated with 2D plans. Eighty-five patients were enrolled in the study group. Review of the 3D datasets led to changes in the target area of interest in 44/85 (52 %) of cases, of which 21/85 (25 %) were clinically significant. 3D plans resulted in superior target coverage and normal tissue sparing. There was no significant difference in patient-reported outcomes however. 3D radiotherapy planning resulted in superior treatment plans but we were unable to demonstrate a significant benefit in clinical outcomes. Prospective study designs are needed to describe the contemporary expectation of palliative radiotherapy for bone metastases in the modern era of 3D planning.

  12. Brain Metastases in Newly Diagnosed Breast Cancer: A Population-Based Study.

    Science.gov (United States)

    Martin, Allison M; Cagney, Daniel N; Catalano, Paul J; Warren, Laura E; Bellon, Jennifer R; Punglia, Rinaa S; Claus, Elizabeth B; Lee, Eudocia Q; Wen, Patrick Y; Haas-Kogan, Daphne A; Alexander, Brian M; Lin, Nancy U; Aizer, Ayal A

    2017-08-01

    Population-based estimates of the incidence and prognosis of brain metastases at diagnosis of breast cancer are lacking. To characterize the incidence proportions and median survivals of patients with breast cancer and brain metastases at the time of cancer diagnosis. Patients with breast cancer and brain metastases at the time of diagnosis were identified using the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute. Data were stratified by subtype, age, sex, and race. Multivariable logistic and Cox regression were performed to identify predictors of the presence of brain metastases at diagnosis and factors associated with all-cause mortality, respectively. For incidence, we identified a population-based sample of 238 726 adult patients diagnosed as having invasive breast cancer between 2010 and 2013 for whom the presence or absence of brain metastases at diagnosis was known. Patients diagnosed at autopsy or with an unknown follow-up were excluded from the survival analysis, leaving 231 684 patients in this cohort. Incidence proportion and median survival of patients with brain metastases and newly diagnosed breast cancer. We identified 968 patients with brain metastases at the time of diagnosis of breast cancer, representing 0.41% of the entire cohort and 7.56% of the subset with metastatic disease to any site. A total of 57 were 18 to 40 years old, 423 were 41 to 60 years old, 425 were 61-80 years old, and 63 were older than 80 years. Ten were male and 958 were female. Incidence proportions were highest among patients with hormone receptor (HR)-negative human epidermal growth factor receptor 2 (HER2)-positive (1.1% among entire cohort, 11.5% among patients with metastatic disease to any distant site) and triple-negative (0.7% among entire cohort, 11.4% among patients with metastatic disease to any distant site) subtypes. Median survival among the entire cohort with brain metastases was 10.0 months. Patients with HR

  13. An analysis of the relationship between metastases and cachexia in lung cancer patients.

    Science.gov (United States)

    Shiono, Masatoshi; Huang, Kan; Downey, Robert J; Consul, Nikita; Villanueva, Nicolas; Beck, Kristen; Fenn, Kathleen; Dietz, Donald; Yamaguchi, Takuhiro; Kato, Shunsuke; Divgi, Chaitanya; Kalinsky, Kevin; Wei, Ying; Zhang, Yuan; Borczuk, Alain C; Inoue, Akira; Halmos, Balazs; Acharyya, Swarnali

    2016-09-01

    Weight loss and hematogenous metastases are poor prognosis factors in lung cancer patients that can but do not necessarily co-occur. We retrospectively investigated the clinical association between cachexia, tumor characteristics (such as metastatic burden and mutational status), and treatment in lung cancer patients. The medical records of 394 lung cancer patients from two institutions (Columbia University, USA and Tohoku University, Japan) were reviewed. Information collected included the presence of cachexia, histologic subtype, tumor stage, number of metastases, mutation status, treatment, and survival. Descriptive statistics were performed. Only stage IV patients exhibited >5% weight loss (0.8%, 2.2%, 3.6%, and 5.1%, for stages I to IV; P = 0.0001). Patients with metastases developed cachexia more often than patients without metastases independent of treatment (6.0% and 7.1% weight loss in patients with metastases vs. 2.5% and 2.0% in patients without metastases, before [P = 0.0001] and after [P cachexia had worse survival than patients without cachexia (hazard ratio, 2.94; 95% confidence interval, 2.08-4.16; P cachexia might be linked intrinsically and are independent of treatments administered. KRAS-mutated tumors were more commonly associated with cachexia. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  14. Study on 41Ca-AMS for diagnosis and assessment of cancer bone metastasis in rats

    Science.gov (United States)

    Shen, Hongtao; Pang, Fangfang; Jiang, Shan; He, Ming; Dong, Kejun; Dou, Liang; Pang, Yijun; Yang, Xianlin; Ruan, Xiangdong; Liu, Manjun; Xia, Chunbo

    2015-10-01

    The annual incidence of new cancer patients in China is about 2 million, 30-40% of which will end up with bone metastasis. Profound study on the preclinical model and early diagnosis of cancer bone metastasis in rats are very significant for the drug development, better understanding and treatment of bone metastases. In order to monitor the process of bone metabolism and early detection of bone metastasis of cancer cells, a technique of 41Ca isotope tracer combined with AMS has been developed and applied in the study on the bone metastasis of cancer cells by rat model. In this work, 3-month-old female Sprague-Dawley (SD) rats were randomly divided into different groups, and tumor cells injected respectively into the tail vein, femoral artery, femoral cavity and the thigh muscle to establish the rat models for bone metastases. The most appropriate model, i.e., the thigh muscle group, was finally adopted in our real metastases experiment. Each rat in this group was intramuscularly (i.m.) injected with 250 μl CaCl2 solution (containing 1.4 mg Ca and 5nCi 41Ca). About 40 days later, the rat mammary gland carcinoma cells (Walker 256) were injected into these rats following the established protocol. After bone metastasis, medicine interventions were performed. The sequential urine and blood samples were collected and analyzed for 41Ca (by AMS) and N-terminal telopeptide (Ntx), respectively. Bone Mineral Density (BMD) values in the femur and the tibia were measured by CT scan. The results of 41Ca/Ca in longitudinal urinary samples can sensitively reveal the skeletal perturbations caused by bone metastasis of rats, suggests that 41Ca might be similarly developed for human use and improve clinical management through the assessment of the curative effect and non-invasive detection of the earliest stages of cancer growth in bone.

  15. Cancer mamma og skjelettmetastaser : Hindrer strålingen videre tumorvekst, og i hvilken grad konsolideres situasjonen i den spongiøse virvelcorpus?

    OpenAIRE

    Kjus, Anne Ragnhild

    2005-01-01

    Cancer mamma and skeletal metastases Abstract written by Anne Ragnhild Kjus, H-00 Background: In human cancers, bone is a predominant site for metastases. It is well known that metastases cause morbidity and mortality in patients with cancer. Breast cancer has a propensity to metastasize to bone. In Norway 2000 women developes breast cancer each year, and the mortality is 750-800 cases. 70% of them suffer from skeletal metastases and the management is palliativ, aimed at providing the...

  16. Incidental Benign Metastasizing Leiomyoma in a Patient with Bone Sarcoma: A Case Report

    Directory of Open Access Journals (Sweden)

    Zanndor Jacob del Real-Romo

    2014-01-01

    Full Text Available Background. The benign metastasizing leiomyoma is an exceptionally rare entity; it presents with ectopic leiomyoma nodules with a benign pattern. Symptoms vary according to the anatomic location. The diagnosis is histopathological, usually in patients with history of hysterectomy. Case Presentation. A 36-year-old female with 2-month history of left knee pain was diagnosed with bone fibrosarcoma. A CT scan showed pulmonary nodules. The patient started neoadjuvant chemotherapy. Conservative surgery of pelvic limb was achieved. A new CT scan reported pulmonary nodules that remained in relation to the previous CT. A nodule resection by thoracotomy and TOB (transoperative biopsy was performed. The final pathology report described benign proliferative lesions consistent with benign metastatic leiomyoma. Conclusions. Benign metastatic leiomyoma is a rare condition presenting with uterine and extrauterine nodules most commonly in the lung. The diagnosis is histopathological. The surgical procedure must be reserved for selected patients.

  17. Prevention and treatment of bone fragility in cancer patient

    Science.gov (United States)

    Ottanelli, Silva

    2015-01-01

    vitamin D. Bisphosphonates and denosumab are used for the management of bone remodeling and bone loss induced by cancer treatments. Bisphosphonates also have anti-tumor effects per se, which are expressed in potentially prevent the development of bone metastases. In men with metastatic prostate cancer and which is induced androgen deprivation, it is usefully used denosumab 120 mg monthly or zoledronic acid 4 mg monthly. PMID:26604936

  18. Distant Cutaneous Metastases of Prostate Cancer: A Report of 2 Cases.

    Science.gov (United States)

    Rodríguez-Lojo, R; Castiñeiras, I; Rey-Sanjurjo, J L; Fernández-Díaz, M L

    2016-09-01

    Cutaneous metastases of prostate cancer are extremely rare. We present 2 cases of distant cutaneous metastases at atypical locations of prostate adenocarcinoma, and highlight the value of 2 immunohistochemical stains-prostatic acid phosphatase and prostate-specific membrane antigen-that can aid diagnosis, particularly in cases with negative staining for prostate-specific antigen. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. [How does we treat liver metastases from colorectal cancer by cure-intent surgery ?].

    Science.gov (United States)

    Takahashi, Keiichi; Yamaguchi, Tatsuro; Nakano, Daisuke; Nakayama, Yujiro; Oohinata, Ryouki; Yajima, Kazuhito; Iwasaki, Yoshiaki; Matsumoto, Hiroshi

    2013-08-01

    Surgery is the most optimal and curative intent strategy for liver recurrence from colorectal cancer. There are scoring systems and grade classification for liver resection. If we carry out preoperative imaging of liver metastases strictly following to liver resection, we can expect to get a cure state satisfactory. Early detection and repeated liver resection improve the outcome of residual liver recurrence after liver resection. The maximum number of liver metastases for cure intent liver resection is unclear. Further examination is necessary.

  20. Management of long bone metastases: recommendations from the Italian Orthopaedic Society bone metastasis study group.

    Science.gov (United States)

    Capanna, Rodolfo; Piccioli, Andrea; Di Martino, Alberto; Daolio, Primo Andrea; Ippolito, Vincenzo; Maccauro, Giulio; Piana, Raimondo; Ruggieri, Pietro; Gasbarrini, Alessandro; Spinelli, Maria Silvia; Campanacci, Domenico Andrea

    2014-10-01

    The purpose of this article is to outline the current approach to patients affected by metastasis to the long bones and to present a clinical and surgical algorithm available for clinicians and for future research. A modern approach to patients affected by long bone metastasis in fact requires a multidisciplinary contest where oncologists, radiotherapists, surgeons and physical therapists cooperate with a shared vision, in order to provide the best possible integrated treatments available. The authors of this article constitute the Bone Metastasis Study Group of the Italian Orthopaedic Society (SIOT): a national group of orthopedic tumor surgeons who are dedicated to studying the approach, techniques and outcomes of surgery for metastatic tumours of the musculoskeletal system.

  1. Locally ablative treatment of breast cancer liver metastases: identification of factors influencing survival (the Mammary Cancer Microtherapy and Interventional Approaches (MAMMA MIA) study).

    Science.gov (United States)

    Seidensticker, Max; Garlipp, Benjamin; Scholz, Sophia; Mohnike, Konrad; Popp, Felix; Steffen, Ingo; Seidensticker, Ricarda; Stübs, Patrick; Pech, Maciej; PowerskI, Maciej; Hass, Peter; Costa, Serban-Dan; Amthauer, Holger; Bruns, Christiane; Ricke, Jens

    2015-07-14

    Liver metastases from breast cancer (LMBC) are typically considered to indicate systemic disease spread and patients are most often offered systemic palliative treatment only. However, retrospective studies suggest that some patients may have improved survival with local treatment of their liver metastases compared to systemic therapy alone. In the absence of randomized trials, it is important to identify patient characteristics indicating that benefit from local treatment can be expected. 59 patients undergoing radiofrequency ablation (RFA), interstitial brachytherapy (BT), or radioembolization (RE) of LMBC as a salvage treatment were studied. Potential factors influencing survival were analyzed in a multivariate Cox model. For factors identified to have an independent survival impact, Kaplan-Meier analysis and comparison of overall survival (OS) using the log-rank test was performed. Median OS following local interventional treatment was 21.9 months. Considering only factors evaluable at treatment initiation, maximum diameter of liver metastases (≥3.9 cm; HR: 3.1), liver volume (≥ 1376 mL; HR: 2.3), and history of prior chemotherapy (≥ 3 lines of treatment; HR: 2.5-2.6) showed an independent survival impact. When follow-up data were included in the analysis, significant factors were maximum diameter of liver metastases (≥ 3.9 cm; HR: 3.1), control of LMBC during follow-up (HR: 0.29), and objective response as best overall response (HR: 0.21). Neither the presence of any extrahepatic metastases nor presence of bone metastases only had a significant survival impact. Median OS was 38.7 vs. 16.1 months in patients with metastases history of systemic LMBC treatment are most likely to benefit from local approaches. Limited extrahepatic disease should not lead to exclusion from a randomized study and should not be a contraindication for local LMBC treatment as long as no randomized data are available.

  2. Photodynamic Molecular Beacons: An Image-Guided Therapeutic Approach to Breast Cancer Vertebral Metastases

    Science.gov (United States)

    2012-03-01

    spinal metastases are predominantly osteolytic (bone destructive), which is associated with an increase in osteo- clast activity.1 Metastasis disrupts...0.001). The distributions and shape of the cells are largely homogeneous after incubation with the beacons, suggesting minimal toxicity (SI Figure S3

  3. Pattern of Colon Cancer Lymph Node Metastases in Patients Undergoing Central Mesocolic Lymph Node Excision

    DEFF Research Database (Denmark)

    Bertelsen, Claus A; Kirkegaard-Klitbo, Anders; Nielsen, Mingyuan

    2016-01-01

    BACKGROUND: Extended mesocolic lymph node dissection in colon cancer surgery seems to improve oncological outcome. A possible reason might be related to metastases in the central mesocolic lymph nodes. OBJECTIVE: The purpose of this study was to describe the pattern of mesocolic lymph node...... not considered appropriate. The risk of central mesocolic lymph node metastases for right-sided cancers varies between 1% and 22%. In sigmoid cancer, the risk is reported in ≤12% of the patients and is associated with advanced T stage. LIMITATIONS: The retrospective design and heterogeneity, in terms...

  4. Use of Animal Models in Understanding Cancer-induced Bone Pain

    Directory of Open Access Journals (Sweden)

    Lauren M. Slosky

    2015-01-01

    Full Text Available Many common cancers have a propensity to metastasize to bone. Although malignancies often go undetected in their native tissues, bone metastases produce excruciating pain that severely compromises patient quality of life. Cancer-induced bone pain (CIBP is poorly managed with existing medications, and its multifaceted etiology remains to be fully elucidated. Novel analgesic targets arise as more is learned about this complex and distinct pain state. Over the past two decades, multiple animal models have been developed to study CIBP's unique pathology and identify therapeutic targets. Here, we review animal models of CIBP and the mechanistic insights gained as these models evolve. Findings from immunocompromised and immunocompetent host systems are discussed separately to highlight the effect of model choice on outcome. Gaining an understanding of the unique neuromolecular profile of cancer pain through the use of appropriate animal models will aid in the development of more effective therapeutics for CIBP.

  5. Bisphosphonate-related atypical femoral fracture with bone metastasis of breast cancer: case report and review.

    Science.gov (United States)

    Hayashi, Kazunori; Aono, Masanari; Shintani, Kousuke; Kazuki, Kenichi

    2014-03-01

    Intravenous bisphosphonates (BPs) have been used to reduce the frequency of skeletal-related events due to bone metastases of several kinds of cancers. Although many studies on BP-related atypical fractures (BRAFs) due to the use of BP for osteoporosis treatment have been reported, few reports on BRAFs arising as a complication of long-term BP use for bone metastasis of cancer are available. A 62-year-old woman with a history of breast cancer presented with right thigh pain after she had a fall. Radiographs indicated a transverse fracture in the shaft of the right femur. She had been on zoledronate treatment for six years. Based on radiographic and histopathological findings, we concluded that the fracture was not a pathological fracture associated with metastasis but was a complication of long-term BP treatment. Clinical oncologists should consider the possibility of BRAFs in patients on long-term zoledronate treatment for bone metastases.

  6. SRC family kinases as novel therapeutic targets to treat breast cancer brain metastases.

    Science.gov (United States)

    Zhang, Siyuan; Huang, Wen-Chien; Zhang, Lin; Zhang, Chenyu; Lowery, Frank J; Ding, Zhaoxi; Guo, Hua; Wang, Hai; Huang, Suyun; Sahin, Aysegul A; Aldape, Kenneth D; Steeg, Patricia S; Yu, Dihua

    2013-09-15

    Despite better control of early-stage disease and improved overall survival of patients with breast cancer, the incidence of life-threatening brain metastases continues to increase in some of these patients. Unfortunately, other than palliative treatments there is no effective therapy for this condition. In this study, we reveal a critical role for Src activation in promoting brain metastasis in a preclinical model of breast cancer and we show how Src-targeting combinatorial regimens can treat HER2(+) brain metastases in this model. We found that Src was hyperactivated in brain-seeking breast cancer cells derived from human cell lines or from patients' brain metastases. Mechanistically, Src activation promoted tumor cell extravasation into the brain parenchyma via permeabilization of the blood-brain barrier. When combined with the EGFR/HER2 dual-targeting drug lapatinib, an Src-targeting combinatorial regimen prevented outgrowth of disseminated breast cancer cells through the induction of cell-cycle arrest. More importantly, this combinatorial regimen inhibited the outgrowth of established experimental brain metastases, prolonging the survival of metastases-bearing mice. Our results provide a rationale for clinical evaluation of Src-targeting regimens to treat patients with breast cancer suffering from brain metastasis. ©2013 AACR.

  7. Concurrent antitumor and bone-protective effects of everolimus in osteotropic breast cancer.

    Science.gov (United States)

    Browne, Andrew J; Kubasch, Marie L; Göbel, Andy; Hadji, Peyman; Chen, David; Rauner, Martina; Stölzel, Friedrich; Hofbauer, Lorenz C; Rachner, Tilman D

    2017-08-09

    The mammalian target of rapamycin inhibitor everolimus is approved as an antitumor agent in advanced estrogen receptor-positive breast cancer. Surrogate bone marker data from clinical trials suggest effects on bone metabolism, but the mode of action of everolimus in bone biology remains unclear. In this study, we assessed potential bone-protective effects of everolimus in the context of osteotropic tumors. The effects of everolimus on cancer cell viability in vitro and on tumor growth in vivo were assessed. Everolimus-regulated osteoclastogenesis and osteoblastogenesis were also assessed in vitro before we assessed the bone-protective effect of everolimus in a model where bone loss was induced in ovariectomized (OVX) mice. Finally, the role of everolimus in the progression of osteolytic bone disease was assessed in an intracardiac model of breast cancer bone metastases. At low concentrations (1 nM) in vitro, everolimus reduced the viability of human and murine cancer cell lines and impaired the osteoclastogenesis of osteoclast progenitors as assessed by quantitative real-time polymerase chain reaction and counting tartrate-resistant acid phosphatase-positive, multinucleated osteoclasts (p < 0.001). Everolimus had little or no deleterious effect on osteoblastogenesis in vitro, with concentrations of 1 and 10 nM increasing the messenger RNA expression of osteoblast marker genes (p ≤ 0.05) and leaving mineralization in differentiated human mesenchymal stem cells unchanged. Everolimus treatment (1 mg/kg body weight/day) prevented the bone loss observed in OVX mice and concurrently inhibited the metastatic growth of MDA-MB-231 cells by 70% (p < 0.002) while preserving bone mass in an intracardiac model of bone metastasis. These results underline the antitumor effects of everolimus and highlight its bone-protective efficacy, warranting further research on the potential implications on bone health in populations prone to osteoporosis and bone metastases

  8. 77 FR 11123 - Scientific Information Request on Local Therapies for Unresectable Colorectal Cancer Metastases...

    Science.gov (United States)

    2012-02-24

    ..., number of patients screened/eligible/enrolled/lost to withdrawn/follow- up/analyzed, and effectiveness... therapies in patients whose disease is refractory to systemic therapy for unresectable colorectal cancer... Therapies for Unresectable Colorectal Cancer Metastases to the Liver AGENCY: Agency for Healthcare Research...

  9. Morphological and phenotypical features of ovarian metastases in breast cancer patients.

    Science.gov (United States)

    Peters, Inge T A; van der Steen, Merle A; Huisman, Bertine W; Hilders, Carina G J M; Smit, Vincent T H B M; Vahrmeijer, Alexander L; Sier, Cornelis F M; Trimbos, J Baptist; Kuppen, Peter J K

    2017-03-21

    Autotransplantation of frozen-thawed ovarian tissue is a method to preserve ovarian function and fertility in patients undergoing gonadotoxic therapy. In oncology patients, the safety cannot yet be guaranteed, since current tumor detection methods can only exclude the presence of malignant cells in ovarian fragments that are not transplanted. We determined the need for a novel detection method by studying the distribution of tumor cells in ovaries from patients with breast cancer. Furthermore, we examined which cell-surface proteins are suitable as a target for non-invasive tumor-specific imaging of ovarian metastases from invasive breast cancer. Using the nationwide database of the Dutch Pathology Registry (PALGA), we identified a cohort of 46 women with primary invasive breast cancer and ovarian metastases. The localization and morphology of ovarian metastases were determined on hematoxylin-and-eosin-stained sections. The following cell-surface markers were immunohistochemically analyzed: E-cadherin, epithelial membrane antigen (EMA), human epidermal growth receptor type 2 (Her2/neu), carcinoembryonic antigen (CEA), αvβ6 integrin and epithelial cell adhesion molecule (EpCAM). The majority of ovarian metastases (71%) consisted of a solitary metastasis or multiple distinct nodules separated by uninvolved ovarian tissue, suggesting that ovarian metastases might be overlooked by the current detection approach. Combining the targets E-cadherin, EMA and Her2/neu resulted in nearly 100% detection of ductal ovarian metastases, whereas the combination of EMA, Her2/neu and EpCAM was most suitable to detect lobular ovarian metastases. Examination of the actual ovarian transplants is recommended. A combination of targets is most appropriate to detect ovarian metastases by tumor-specific imaging.

  10. Fractionated half body irradiation for palliation of multiple symptomatic bone metastases from solid tumors

    Energy Technology Data Exchange (ETDEWEB)

    Sekiguchi, Kenji; Hayashi, Shinya; Sunagawa, Yoshimitsu; Sougawa, Mitsuharu; Nakazawa, Masanori; Yamashita, Takashi (Japanese Foundation for Cancer Research, Tokyo (Japan). Hospital)

    1992-06-01

    This was a phase I-II nonrandomized study that explored the toxicity and response of fractionated half-body irradiation (F-HBI) in patients with multiple symptomatic osseous metastases. The patients had no premedication and received 10 Gy in 5 fractions with a dose rate of 15 cGy/min. At the Cancer Institute Hospital, 9 patients were treated by this technique (1 upper and lower F-HBI, 6 upper F-HBI, 2 lower F-HBI). All patients were female and had adenocarcinomas (8 breast and 1 lung). Adverse effects were myelosuppression, vomiting and partial alopecia. But hematologic toxicity was treated with blood transfusion or G-CSF. All toxicity was transient, and no pneumonitis nor radiation-related deaths occurred. When given as palliation, F-HBI was found to relieve pain in 80% of the patients. In 10% of the patients the pain relief was complete. The mean time to achieve pain relief in responders after F-HBI was 9 days. The pain relief was long-lasting and continued without need of reirradiation for 40% of the remaining patient's life. This treatment modality appears to be well tolerated and effective in patients with multiple symptomatic osseous metastases. The optimal indications, dose and fractionation for F-HBI should be further explored in randomized trials. (author).

  11. From Breast to Bone: Tracking Gene Expression Changes Responsible for Breast Cancer Metastasis in a Humanized Mouse Model with Molecular Imaging

    Science.gov (United States)

    2015-11-01

    amplification) breast cancer (TNBC) is an aggressively metastatic subtype that preferentially metastasizes to visceral organs including the lungs...Determination of the transcriptome of breast cancer cells that selectively home to the lungs and bones. P.2 lung metastases and corresponding mammary...Troester MA, Herschkowitz JI, Oh DS, He X, Hoadley KA, Barbier CS, Perou CM. Gene expression patterns associated with p53 status in breast cancer . BMC

  12. Biological resonance for cancer metastasis, a new hypothesis based on comparisons between primary cancers and metastases.

    Science.gov (United States)

    Gao, Dongwei; Li, Sha

    2013-12-01

    Many hypotheses have been proposed to try to explain cancer metastasis. However, they seem to be contradictory and have some limitations. Comparisons of primary tumors and matched metastases provide new insight into metastasis. The results show high concordances and minor differences at multiple scales from organic level to molecular level. The concordances reflect the commonality between primary cancer and metastasis, and also mean that metastatic cancer cells derived from primary cancer are quite conservative in distant sites. The differences reflect variation that cancer cells must acquire new traits to adapt to foreign milieu during the course of evolving into a new tumor in second organs. These comparisons also provided new information on understanding mechanism of vascular metastasis, organ-specific metastasis, and tumor dormancy. The collective results suggest a new hypothesis, biological resonance (bio-resonance) model. The hypothesis has two aspects. One is that primary cancer and matched metastasis have a common progenitor. The other is that both ancestors of primary cancer cells and metastatic cancer cells are under similar microenvironments and receive similar or same signals. When their interactions reach a status similar to primary cancer, metastasis will occur. Compared with previous hypotheses, the bio-resonance hypothesis seems to be more applicable for cancer metastasis to explain how, when and where metastasis occurs. Thus, it has important implications for individual prediction, prevention and treatment of cancer metastasis.

  13. SPECIFIC CHARACTERISTICS OF BRAIN METASTASIZING IN PATIENTS WITH LUMINAL SUBTYPE OF BREAST CANCER

    Directory of Open Access Journals (Sweden)

    A. S. Balkanov

    2016-01-01

    Full Text Available Background: More than half of female patients with breast cancer are diagnosed with a  luminal subtype of the disease; however, specific characteristics of its metastases to the brain have been not well studied, unlike those of HER2 positive and triple negative subtypes. Aim: A  comparative analysis of characteristics of metastatic brain lesions in patients with luminal breast cancer. Materials and methods: The time from surgery for breast cancer to the first recurrence and to metastatic brain lesions (assessed by contrast-enhanced MRI imaging was measured in 41 patients with luminal subtype of breast cancer (median age, 49.5±9.6  years, depending on a  diameter of the primary tumor and numbers of involved axillary lymph nodes. Results: The time interval to occurrence of brain metastases in luminal subtype of breast cancer is not associated with the size of the tumor. If≥4  axillary lymph nodes are involved (N2–3, brain metastases are identified much earlier (p<0.05 than in patients with N0–1 (34.5±23.9 months and 62.7±50 months, respectively. Neither the size nor the involvement of axillary lymph nodes has any impact on the rates of metastatic lesion to the brain during the first recurrence. Conclusion: Brain metastases occur at a much shorter time in those patients of luminal subtype of breast cancer who have metastases in≥4  axillary lymph nodes. Brain metastases develop in 50% of patients with the first recurrence of the luminal subtype of breast cancer.

  14. [A 65-year-old man with liver metastases after lung cancer resection that responded to concomitant use of gemcitabine and carboplatin].

    Science.gov (United States)

    Kawabe, Masakazu; Sasaki, Masato; Hirai, Seiya; Ikeda, Takeshi; Sasaki, Hisashi; Yoshida, Makoto; Amaya, Hirokazu; Aotake, Toshiharu; Uchinami, Masaru; Ihaya, Akio; Tanaka, Kuniyoshi

    2006-01-01

    A 65-year-old male with liver metastases after lung cancer resection was treated with five courses of chemotherapy consisting of gemcitabine (GEM) 1,000 mg/m2 (day 1, 8, every 4 weeks) plus carboplatin (CBDCA) AUC 6 (day 1, every 4 weeks). A partial response (PR) was achieved, his symptoms abated and his quality of life(QOL) improved. Although bone marrow suppression was observed as a side effect, it was within the tolerable range and did not interfere with therapy. This approach may be worth considering as a first-line anti-cancer chemotherapy for recurrence lung cancer.

  15. Modeling selective elimination of quiescent cancer cells from bone marrow.

    Science.gov (United States)

    Cavnar, Stephen P; Rickelmann, Andrew D; Meguiar, Kaille F; Xiao, Annie; Dosch, Joseph; Leung, Brendan M; Cai Lesher-Perez, Sasha; Chitta, Shashank; Luker, Kathryn E; Takayama, Shuichi; Luker, Gary D

    2015-08-01

    Patients with many types of malignancy commonly harbor quiescent disseminated tumor cells in bone marrow. These cells frequently resist chemotherapy and may persist for years before proliferating as recurrent metastases. To test for compounds that eliminate quiescent cancer cells, we established a new 384-well 3D spheroid model in which small numbers of cancer cells reversibly arrest in G1/G0 phase of the cell cycle when cultured with bone marrow stromal cells. Using dual-color bioluminescence imaging to selectively quantify viability of cancer and stromal cells in the same spheroid, we identified single compounds and combination treatments that preferentially eliminated quiescent breast cancer cells but not stromal cells. A treatment combination effective against malignant cells in spheroids also eliminated breast cancer cells from bone marrow in a mouse xenograft model. This research establishes a novel screening platform for therapies that selectively target quiescent tumor cells, facilitating identification of new drugs to prevent recurrent cancer. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Application of conditional probability analysis to distant metastases from lung cancer.

    Science.gov (United States)

    Oikawa, Akihiro; Takahashi, Hideto; Ishikawa, Hiroichi; Kurishima, Koichi; Kagohashi, Katsunori; Satoh, Hiroaki

    2012-03-01

    The aim of this study was to reveal whether there was non-randomness in the occurrence of metastasis and, if the non-randomness was denied, whether there were specific metastatic patterns in lung cancer patients. Patients who presented with pathologically diagnosed lung cancer between January 1986 and March 2009 at our hospitals were included. A statistical method and conditional probability analysis were used to analyze the data. Under the condition of one metastatic organ A (lung, bone, brain, liver or adrenal gland; the 5 most common metastatic organs), we determined the conditional probability of distant metastasis to a specific organ B, which was written as P(B | A), and compared it with the probability of distant metastasis P(B). The study group consisted of 1,994 patients. Of the 1,994 patients, 839 (42.1%) had distant metastases at the time of the initial diagnosis of lung cancer. With the exception of the comparisons between P(lung) and P(lung | adrenal gland) and between P(adrenal gland) and P(adrenal gland | lung), there were statistically significant differences between P(B | A) and P(B) in the 5 metastatic organs. In addition, P(B | A) and P(C | B | A) varied according to each organ and P(confined to A), P(confined to A and B) and P(confined to A, B and C) were different in each metastatic organ. In lung cancer patients, distant metastasis occurred non-randomly and there may be certain specific patterns of distant metastasis. The accumulation of knowledge of specific patterns of metastasis may aid the approach to individualized treatments.

  17. Improving the dose-myelotoxicity correlation in radiometabolic therapy of bone metastases with {sup 153}Sm-EDTMP

    Energy Technology Data Exchange (ETDEWEB)

    Pacilio, Massimiliano; Basile, Chiara [Azienda Ospedaliera San Camillo Forlanini, Rome (Italy). Dept. of Medical Physics; Ventroni, Guido; Mango, Lucio [Azienda Ospedaliera San Camillo Forlanini, Rome (Italy). Dept. of Nuclear Medicine; Ialongo, Pasquale [Azienda Ospedaliera San Camillo Forlanini, Rome (Italy). Dept. of Radiology; Becci, Domenico [University of Rome, Health Physics Postgraduate School, Rome (Italy)

    2014-02-15

    {sup 153}Sm-ethylene diamine tetramethylene phosphonic acid ({sup 153}Sm-EDTMP) is widely used to palliate pain from bone metastases, and is being studied for combination therapy beyond palliation. Conceptually, red marrow (RM) dosimetry allows myelotoxicity to be predicted, but the correlation is poor due to dosimetric uncertainty, individual sensitivity and biological effects from previous treatments. According to EANM guidelines, basic dosimetric procedures have been studied to improve the correlation between dosimetry and myelotoxicity in {sup 153}Sm-EDTMP therapy. RM dosimetry for 33 treatments of bone metastases from breast, prostate and lung tumours was performed prospectively (with {sup 99m}Tc-MDP) and retrospectively, acquiring whole-body scans early and late after injection. The {sup 153}Sm-EDTMP activity was calculated by prospective dosimetry based on measured skeletal uptake and full physical retention, with the RM absorbed dose not exceeding 3.8 Gy. Patient-specific RM mass was evaluated by scaling in terms of body weight (BW), lean body mass (LBM) and trabecular volume (TV) estimated from CT scans of the L2-L4 vertebrae. Correlations with toxicity were determined in a selected subgroup of 27 patients, in which a better correlation between dosimetry and myelotoxicity was expected. Skeletal uptakes of {sup 99m}Tc and {sup 153}Sm (Tc{sub %} and Sm{sub %}) were well correlated. The median Sm{sub %} was higher in prostate cancer (75.3 %) than in lung (60.5 %, p = 0.005) or breast (60.8 %, p = 0.008). PLT and WBC nadirs were not correlated with administered activity, but were weakly correlated with uncorrected RM absorbed doses, and the correlation improved after rescaling in terms of BW, LBM and TV. Most patients showed transient toxicity (grade 1-3), which completely and spontaneously recovered over a few days. Using TV, RM absorbed dose was in the range 2-5 Gy, with a median of 312 cGy for PLT in patients with toxicity and 247 cGy in those with no

  18. Referral patterns of patients with liver metastases due to colorectal cancer for resection.

    LENUS (Irish Health Repository)

    Al-Sahaf, O

    2012-02-01

    INTRODUCTION: Colorectal carcinoma accounts for 10% of cancer deaths in the Western World, with the liver being the most common site of distant metastases. Resection of liver metastases is the treatment of choice, with a 5-year survival rate of 35%. However, only 5-10% of patients are suitable for resection at presentation. AIMS: To examine the referral pattern of patients with liver metastases to a specialist hepatic unit for resection. METHODOLOGY: Retrospective review of patient\\'s charts diagnosed with colorectal liver metastases over a 10-year period. RESULTS: One hundred nine (38 women, 71 men) patients with liver metastases were included, mean age 61 years; 79 and 30 patients had synchronous and metachronus metastases, respectively. Ten criteria for referral were identified; the referral rate was 8.25%, with a resection rate of 0.9%. Forty two percent of the patients had palliative chemotherapy; 42% had symptomatic treatment. CONCLUSION: This study highlights the advanced stage of colorectal cancer at presentation; in light of modern evidence-based, centre-oriented therapy of liver metastasis, we conclude that criteria of referral for resection should be based on the availability of treatment modalities.

  19. Long-term Survivors After Liver Resection for Breast Cancer Liver Metastases.

    Science.gov (United States)

    BacalbaȘa, Nicolae; Balescu, Irina; Dima, Simona; Popescu, Irinel

    2015-12-01

    Although breast cancer liver metastases are considered a sign of systemic recurrence and are considered a poor prognostic factor that transforms the patient into a candidate for palliative chemotherapy, surgery might be performed with good results. Success reported after liver resection for colorectal hepatic metastases encouraged the oncological surgeon to apply similar protocols in breast cancer liver metastases. Data of patients submitted to hepatectomies for breast cancer liver metastases in the "Dan Setlacec" Center of Gastrointestinal Disease and Liver Transplantation, Fundeni Clinical Institute, Bucharest were retrospectively reviewed. Among five cases survival after liver surgery surpassed 5 years and was considered long-term survival. One of the five cases was submitted to a second liver resection. Most often long-term survivors were reported among patients with single, metachronous and smaller than 5-cm lesions. In selected cases liver resection for breast cancer liver metastases can be associated with a significant increase in survival. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  20. Limited heterogeneity of known driver gene mutations among the metastases of individual patients with pancreatic cancer.

    Science.gov (United States)

    Makohon-Moore, Alvin P; Zhang, Ming; Reiter, Johannes G; Bozic, Ivana; Allen, Benjamin; Kundu, Deepanjan; Chatterjee, Krishnendu; Wong, Fay; Jiao, Yuchen; Kohutek, Zachary A; Hong, Jungeui; Attiyeh, Marc; Javier, Breanna; Wood, Laura D; Hruban, Ralph H; Nowak, Martin A; Papadopoulos, Nickolas; Kinzler, Kenneth W; Vogelstein, Bert; Iacobuzio-Donahue, Christine A

    2017-03-01

    The extent of heterogeneity among driver gene mutations present in naturally occurring metastases-that is, treatment-naive metastatic disease-is largely unknown. To address this issue, we carried out 60× whole-genome sequencing of 26 metastases from four patients with pancreatic cancer. We found that identical mutations in known driver genes were present in every metastatic lesion for each patient studied. Passenger gene mutations, which do not have known or predicted functional consequences, accounted for all intratumoral heterogeneity. Even with respect to these passenger mutations, our analysis suggests that the genetic similarity among the founding cells of metastases was higher than that expected for any two cells randomly taken from a normal tissue. The uniformity of known driver gene mutations among metastases in the same patient has critical and encouraging implications for the success of future targeted therapies in advanced-stage disease.

  1. Pseudo-Meigs' syndrome secondary to metachronous ovarian metastases from transverse colon cancer.

    Science.gov (United States)

    Kyo, Kennoki; Maema, Atsushi; Shirakawa, Motoaki; Nakamura, Toshio; Koda, Kenji; Yokoyama, Hidetaro

    2016-05-14

    Pseudo-Meigs' syndrome associated with colorectal cancer is extremely rare. We report here a case of pseudo-Meigs' syndrome secondary to metachronous ovarian metastases from colon cancer. A 65-year-old female with a history of surgery for transverse colon cancer and peritoneal dissemination suffered from metachronous ovarian metastases during treatment with systemic chemotherapy. At first, neither ascites nor pleural effusion was observed, but she later complained of progressive abdominal distention and dyspnea caused by rapidly increasing ascites and pleural effusion and rapidly enlarging ovarian metastases. Abdominocenteses were repeated, and cytological examinations of the fluids were all negative for malignant cells. We suspected pseudo-Meigs' syndrome, and bilateral oophorectomies were performed after thorough informed consent. The patient's postoperative condition improved rapidly after surgery. We conclude that pseudo-Meigs' syndrome should be included in the differential diagnosis of massive or rapidly increasing ascites and pleural effusion associated with large or rapidly enlarging ovarian tumors.

  2. Quality of Life After Palliative Radiation Therapy for Patients With Painful Bone Metastases: Results of an International Study Validating the EORTC QLQ-BM22

    Energy Technology Data Exchange (ETDEWEB)

    Zeng Liang [Department of Radiation Oncology, Odette Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Chow, Edward, E-mail: edward.chow@sunnybrook.ca [Department of Radiation Oncology, Odette Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Bedard, Gillian; Zhang, Liying [Department of Radiation Oncology, Odette Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Fairchild, Alysa [Department of Radiation Oncology, Cross Cancer Institute, Edmonton, Alberta (Canada); Vassiliou, Vassilios [Department of Radiation Oncology, Bank of Cyprus Oncology Centre, Nicosia (Cyprus); Alm El-Din, Mohamed A. [Department of Clinical Oncology, Tanta University Hospital, Tanta Faculty of Medicine, Tanta (Egypt); Jesus-Garcia, Reynaldo [Department of Orthopedic Oncology, Federal University of Sao Paulo, Sao Paulo (Brazil); Kumar, Aswin [Division of Gynaecology and Genitourinary Oncology, Department of Radiation Oncology, Regional Cancer Center, Trivandrum (India); Forges, Fabien [Inserm CIE3, Saint Etienne University Hospital, Saint-Etienne (France); Unit of Clinical Research, Innovation, and Pharmacology, Saint Etienne University Hospital, Saint-Etienne (France); Tseng, Ling-Ming [Department of Surgery, Taipei Veterans General Hospital, National Yang-Ming University, Taipei, Taiwan (China); Hou, Ming-Feng [Department of Gastroenterologic Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan (China); Chie, Wei-Chu [Department of Public Health and Institute of Epidemiology and Preventative Medicine, National Taiwan University, Taipei, Taiwan (China); Bottomley, Andrew [European Organisation for Research and Treatment of Cancer, EORTC Headquarters, Brussels (Belgium)

    2012-11-01

    Purpose: Radiation therapy (RT) is an effective method of palliating painful bone metastases and can improve function and reduce analgesic requirements. In advanced cancer patients, quality of life (QOL) is the primary outcome of interest over traditional endpoints such as survival. The purpose of our study was to compare bone metastasis-specific QOL scores among patients who responded differently to palliative RT. Methods and Materials: Patients receiving RT for bone metastases across 6 countries were prospectively enrolled from March 2010-January 2011 in a trial validating the QLQ-BM22 and completed the QLQ-BM22 and the core measure (QLQ-C30) at baseline and after 1 month. Pain scores and analgesic intake were recorded, and response to RT was determined according to the latest published guidelines. The Kruskal-Wallis nonparametric and Wilcoxon rank sum tests compared changes in QOL among response groups. A Bonferroni-adjusted P<.003 indicated statistical significance. Results: Of 79 patients who received palliative RT, 59 were assessable. Partial response, pain progression, and indeterminate response were observed in 22, 8, and 29 patients, respectively; there were no patients with a complete response. Patients across all groups had similar baseline QOL scores apart from physical functioning (patients who progressed had better initial functioning). One month after RT, patients who responded had significant improvements in 3 of 4 QLQ-BM22 domains (painful site, P<.0001; painful characteristic, P<.0001; and functional interference, P<.0001) and 3 QLQ-C30 domains (physical functioning, P=.0006; role functioning, P=.0026; and pain, P<.0001). Patients with progression in pain had significantly worse functional interference (P=.0007) and pain (P=.0019). Conclusions: Patients who report pain relief after palliative RT also have better QOL with respect to bone metastasis-specific issues. The QLQ-BM22 and QLQ-C30 are able to discriminate among patients with varying

  3. Influence of the Different Primary Cancers and Different Types of Bone Metastasis on the Lesion-based Artificial Neural Network Value Calculated by a Computer-aided Diagnostic System,BONENAVI, on Bone Scintigraphy Images

    Directory of Open Access Journals (Sweden)

    TAKURO ISODA

    2017-01-01

    Full Text Available Objective(s: BONENAVI, a computer-aided diagnostic system, is used in bone scintigraphy. This system provides the artificial neural network (ANN and bone scan index (BSI values. ANN is associated with the possibility of bone metastasis, while BSI is related to the amount of bone metastasis. The degree of uptake on bone scintigraphy can be affected by the type of bone metastasis. Therefore, the ANN value provided by BONENAVI may be influenced by the characteristics of bone metastasis. In this study, we aimed to assess the relationship between ANN value and characteristics of bone metastasis. Methods: We analyzed 50 patients (36 males, 14 females; age range: 42–87 yrs, median age: 72.5 yrs with prostate, breast, or lung cancer who had undergone bone scintigraphy and were diagnosed with bone metastasis (32 cases of prostate cancer, nine cases of breast cancer, and nine cases of lung cancer. Those who had received systematic therapy over the past years were excluded. Bone metastases were diagnosed clinically, and the type of bone metastasis (osteoblastic, mildly osteoblastic,osteolytic, and mixed components was decided visually by the agreement of two radiologists. We compared the ANN values (case-based and lesion-based among the three primary cancers and four types of bone metastasis.Results: There was no significant difference in case-based ANN values among prostate, breast, and lung cancers. However, the lesion-based ANN values were the highest in cases with prostate cancer and the lowest in cases of lung cancer (median values: prostate cancer, 0.980; breast cancer, 0.909; and lung cancer, 0.864. Mildly osteoblastic lesions showed significantly lower ANN values than the other three types of bone metastasis (median values: osteoblastic, 0.939; mildly osteoblastic, 0.788; mixed type, 0.991; and osteolytic, 0.969. The possibility of a lesion-based ANN value below 0.5 was 10.9% for bone metastasis in prostate cancer, 12.9% for breast cancer, and 37

  4. Influence of the Different Primary Cancers and Different Types of Bone Metastasis on the Lesion-based Artificial Neural Network Value Calculated by a Computer-aided Diagnostic System, BONENAVI, on Bone Scintigraphy Images.

    Science.gov (United States)

    Isoda, Takuro; BaBa, Shingo; Maruoka, Yasuhiro; Kitamura, Yoshiyuki; Tahara, Keiichiro; Sasaki, Masayuki; Hatakenaka, Masamitsu; Honda, Hiroshi

    2017-01-01

    BONENAVI, a computer-aided diagnostic system, is used in bone scintigraphy. This system provides the artificial neural network (ANN) and bone scan index (BSI) values. ANN is associated with the possibility of bone metastasis, while BSI is related to the amount of bone metastasis. The degree of uptake on bone scintigraphy can be affected by the type of bone metastasis. Therefore, the ANN value provided by BONENAVI may be influenced by the characteristics of bone metastasis. In this study, we aimed to assess the relationship between ANN value and characteristics of bone metastasis. We analyzed 50 patients (36 males,14 females; age range: 87-42 yrs median age:72.5 yrs) with prostate, breast, or lung cancer who had undergone bone scintigraphy and were diagnosed with bone metastasis (32 cases of prostate cancer, nine cases of breast cancer, and nine cases of lung cancer). Those who had received systematic therapy over the past years were excluded. Bone metastases were diagnosed clinically, and the type of bone metastasis (osteoblastic, mildly osteoblastic, osteolytic, and mixed components) was decided visually by the agreement of two radiologists. We compared the ANN values (case-based and lesion-based) among the three primary cancers and four types of bone metastasis. There was no significant difference in case-based ANN values among prostate, breast, and lung cancers. However, the lesion-based ANN values were the highest in cases with prostate cancer and the lowest in cases of lung cancer (median values: prostate cancer, 0.980; breast cancer 0.909; and lung cancer, 0.864). Mildly osteoblastic lesions showed significantly lower ANN values than the other three types of bone metastasis (median values: osteoblastic,; 0.939 mildly osteoblastic; 0.788, mixed type; 0.991, and osteolytic. 0.969) The possibility of a lesion-based ANN value below 0.5 was %10.9 for bone metastasis in prostate cancer, %12.9 for breast cancer, and %37.2 for lung cancer. The corresponding

  5. Intrahepatic and systemic therapy with oxaliplatin combined with capecitabine in patients with hepatic metastases from breast cancer

    DEFF Research Database (Denmark)

    Nielsen, D L; Nørgaard, H; Weber Vestermark, Lene

    2012-01-01

    The aim was to evaluate activity and toxicity of hepatic arterial infusion of oxaliplatin in combination with capecitabine in patients with metastatic breast cancer with liver metastases and limited extrahepatic disease.......The aim was to evaluate activity and toxicity of hepatic arterial infusion of oxaliplatin in combination with capecitabine in patients with metastatic breast cancer with liver metastases and limited extrahepatic disease....

  6. Brain-only metastases of small cell lung cancer; efficacy of whole brain radiotherapy. An EORTC phase II study

    NARCIS (Netherlands)

    Postmus, PE; Haaxma-Reiche, H; Gregor, A; Groen, HJM; Lewinski, T; Scolard, T; Kirkpatrick, A; Curran, D; Sahmoud, T; Giaccone, G

    Background and purpose: To evaluate the efficacy of WBRT as a single treatment modality in patients with brain metastases of small cell lung cancer. Patients and methods: The patients had brain metastases of small cell lung cancer without any sign of tumour outside the brain and were treated with 10

  7. WNT5A and Its Receptors in the Bone-Cancer Dialogue.

    Science.gov (United States)

    Thiele, Stefanie; Rachner, Tilman D; Rauner, Martina; Hofbauer, Lorenz C

    2016-08-01

    Wnt signaling is critical for tumorigenesis and skeletal remodeling. However, its contribution to the formation of metastatic bone lesions remains poorly defined. One major challenge of unraveling its role in cancer progression is the high complexity of Wnt signaling, which includes numerous ligands, receptors, and inhibitors, with intricate biological effects and specific signaling pathways depending on the cellular context. In this perspective, we summarize the role of the noncanonical Wnt ligand WNT5A in the development and metastatic process of osteotropic cancer entities. We focus on its tumor-suppressive function in breast cancer, tumor promoting effects in melanoma, and ambiguous role in prostate cancer, and discuss potential challenges and opportunities that may be associated with targeting Wnt signaling for cancer therapy and treatment of bone metastases. © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and Mineral Research.

  8. Synchronous Orbital and Gastrointestinal Metastases from Breast Cancer: A Case Report and Review of Literature

    Directory of Open Access Journals (Sweden)

    Ramawad Soobrah

    2015-01-01

    Full Text Available Breast cancer is the most common malignancy among women and is a significant cause of morbidity and mortality worldwide. With the advent of improved imaging techniques and screening programmes, only a small proportion of women present with metastatic disease. Metastases involving the gastrointestinal (GI tract and orbit are rare occurrences. We describe the case of a woman with simultaneous GI and orbital metastases from breast cancer who initially presented with abdominal pain and blurred vision and also summarise a review of the literature.

  9. Metastases From Colorectal Cancer Avid on 68Ga-PSMA PET/CT

    DEFF Research Database (Denmark)

    Hangaard, Lise; Jochumsen, Mads Ryø; Vendelbo, Mikkel Holm

    2017-01-01

    Ga-PSMA PET/CT is currently used for detection of prostate cancer including metastases, even at low prostate-specific antigen values. A grown number of reports have shown increased uptake of PSMA in neovessels of nonprostatic malignancies including lung cancer, and recently a case report has demo...... demonstrated increased PSMA uptake in colorectal adenocarcinoma. In this case report, we demonstrate increased Ga-PMSA uptake on PET/CT in metastases from previously treated colon adenocarcinoma, and it illustrates the importance of histology of suspicious lesions on Ga-PSMA PET/CT....

  10. CURRENT POSSIBILITIES OF TREATMENT FOR VISCERAL METASTASES IN PATIENTS WITH METASTATIC CASTRATION-REFRACTORY PROSTATE CANCER

    Directory of Open Access Journals (Sweden)

    A. V. Govorov

    2014-07-01

    Full Text Available Medications increasing the survival of patients with metastatic castration-refractory prostate cancer (CRPC are lacking today. In the past 3 years, in the pharmaceutical market there have been a few novel drugs to treat progressive prostate cancer. Abiraterone acetate is an androgen synthesis inhibitor, which is also used to increase the survival of patients with metastatic CRPC that progresses after chemotherapy. The results of treatment for metastatic CRPC depend on a number of factors. Visceral metastases are poor predictors of the course of the disease. The results of abiraterone acetate treatment were analyzed in CRPC patients with visceral metastases.

  11. The influence of orthopedic corsets on the incidence of pathological fractures in patients with spinal bone metastases after radiotherapy.

    Science.gov (United States)

    Rief, Harald; Förster, Robert; Rieken, Stefan; Bruckner, Thomas; Schlampp, Ingmar; Bostel, Tilman; Debus, Jürgen

    2015-10-20

    Clinical care of unstable spinal bone metastases in many centers often includes patient immobilization by means of an orthopedic corset in order to prevent pathological fractures. The aim of this retrospective analysis was to evaluate the incidence of pathological fractures after radiotherapy (RT) in patients with and without orthopedic corsets and to assess prognostic factors for pathological fractures in patients with spinal bone metastases. The incidence of pathological fractures in 915 patients with 2.195 osteolytic metastases in the thoracic and lumbar spine was evaluated retrospectively on the basis of computed tomography (CT) scans between January 2000 and January 2012 depending on prescription and wearing of patient-customized orthopedic corsets. In the corset group, 6.8 and 8.0 % in no-corset group showed pathological fractures prior to RT, no significant difference between groups was detected (p = 0.473). After 6 months, patients in the corset group showed pathological fractures in 8.6 % and in no-corset group in 9.3 % (p = 0.709). The univariate and bivariate analyses demonstrated no significant prognostic factor for incidence of pathological fractures in both groups. In this analysis, we could show for the first time in more than 900 patients, that abandoning a general corset supply in patients with spinal metastases does not significantly cause increased rates of pathological fractures. Importantly, the incidence of pathological fracture after RT was small.

  12. Prediction of lymph node metastases in vulvar cancer: a review.

    NARCIS (Netherlands)

    Oonk, M.H.; Hollema, H.; Hullu, J.A. de; Zee, A.G. van der

    2006-01-01

    The aim of this study was to review the literature on currently available non- and minimally-invasive diagnostic methods and analysis of primary tumor characteristics for prediction of inguinofemoral lymph node metastases in patients with primary squamous cell carcinoma of the vulva. We used the

  13. FGFR3 expression in primary invasive bladder cancers and matched lymph node metastases.

    Science.gov (United States)

    Turo, Rafal; Harnden, Patricia; Thygesen, Helene; Fleischmann, Achim; Thalmann, George N; Seiler, Roland; Cross, William R; Knowles, Margaret A

    2015-01-01

    FGFR3 is considered a good therapeutic target for bladder cancer. However, to our knowledge it is unknown whether the FGFR3 status of primary tumors is a surrogate for related metastases, which must be targeted by FGFR targeted systemic therapies. We assessed FGFR3 protein expression in primary bladder tumors and matched nodal metastases. We examined matched primary tumor and nodal metastases from 150 patients with bladder cancer clinically staged as N0M0. Four samples per patient were incorporated into a tissue microarray and FGFR3 expression was assessed by immunohistochemistry. FGFR3 expression was tested for an association with categorical clinical data using the Fisher exact test, and with overall and recurrence-free survival by Kaplan-Meier analysis. Duplicate spots from primary tumors and lymph node metastases were highly concordant (OR 8.6 and 16.7, respectively, each p FGFR3 expression levels in 79 matched primary tumor and metastasis specimens was high (OR 8.45, p FGFR3 expression. FGFR3 expression in matched primary and metastasized bladder cancer specimens showed good but not absolute concordance. Thus, in most patients primary tumor FGFR3 status can guide the selection of FGFR targeted therapy. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  14. Autocrine inhibition of the c-fms proto-oncogene reduces breast cancer bone metastasis assessed with in vivo dual-modality imaging.

    Science.gov (United States)

    Jeffery, Justin J; Lux, Katie; Vogel, John S; Herrera, Wynetta D; Greco, Stephen; Woo, Ho-Hyung; AbuShahin, Nisreen; Pagel, Mark D; Chambers, Setsuko K

    2014-04-01

    Breast cancer cells preferentially home to the bone microenvironment, which provides a unique niche with a network of multiple bidirectional communications between host and tumor, promoting survival and growth of bone metastases. In the bone microenvironment, the c-fms proto-oncogene that encodes for the CSF-1 receptor, along with CSF-1, serves as one critical cytokine/receptor pair, functioning in paracrine and autocrine fashion. Previous studies concentrated on the effect of inhibition of host (mouse) c-fms on bone metastasis, with resulting decrease in osteolysis and bone metastases as a paracrine effect. In this report, we assessed the role of c-fms inhibition within the tumor cells (autocrine effect) in the early establishment of breast cancer cells in bone and the effects of this early c-fms inhibition on subsequent bone metastases and destruction. This study exploited a multidisciplinary approach by employing two non-invasive, in vivo imaging methods to assess the progression of bone me