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Bone Metastases Prostate cancer

Erika Azorín-Vega, Eva Rojas-Calderón, Guillermina Ferro-Flores, Liliana Aranda-Lara, Nallely Jiménez-Mancilla, Miguel A Nava-Cabrera
This research aimed to assess the radiation absorbed dose produced by 177 Lu-iPSMA (177 Lu-prostate specific membrane antigen inhibitor), 225 Ac-iPSMA and 223 RaCl2 to prostate cancer cell nuclei in a simplified model of bone by using an experimental in-vitro prostate cancer LNCaP cell biokinetic study and Monte Carlo simulation with the MCNPX code. Results showed that 225 Ac-iPSMA releases a nine hundred-fold radiation dose greater than 177 Lu-iPSMA and 14 times more than 223 RaCl2 per unit of activity retained in bone...
January 29, 2019: Applied Radiation and Isotopes
Eugenio Zoni, Letizia Astrologo, Charlotte K Y Ng, Salvatore Piscuoglio, Janine Melsen, Joel Grosjean, Irena Klima, Lanpeng Chen, Ewa B Snaar-Jagalska, Kenneth Flanagan, Gabri van der Pluijm, Peter Kloen, Marco G Cecchini, Marianna Kruithof-de-Julio, George N Thalmann
Prostate Cancer (PCa) is the most common cancer and the second leading cause of cancer-related death in males. When PCa acquires castration resistance, incurable metastases, primarily in the bone, occur. The aim of this study is to test the applicability of targeting MCAM (CD146) with a monoclonal antibody for the treatment of lytic PCa bone metastasis. We evaluated the effect of targeting MCAM using in vivo preclinical bone metastasis models and an in vitro bone niche co-culture system. We utilized FACS, cell proliferation assays, and gene expression profiling to study the phenotype and function of MCAM knockdown in vitro and in vivo...
February 11, 2019: Molecular Cancer Research: MCR
Guillaume Rieunier, Xiaoning Wu, Valentine M Macaulay, Adrian V Lee, Ulrike Weyer-Czernilofsky, Thomas Bogenrieder
Bone metastases are a frequent complication of cancer that are associated with considerable morbidity. Current treatments may temporarily palliate the symptoms of bone metastases, but often fail to delay their progression. Bones provide a permissive environment because they are characterized by dynamic turnover, secreting factors required for bone maintenance but also stimulating the establishment and growth of metastases. Insulin-like growth factors (IGFs) are the most abundant growth factors in bone and are required for normal skeletal development and function...
February 11, 2019: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Matthew Smith, Chris Parker, Fred Saad, Kurt Miller, Bertrand Tombal, Quan Sing Ng, Martin Boegemann, Vsevolod Matveev, Josep Maria Piulats, Luis Eduardo Zucca, Oleg Karyakin, Go Kimura, Nobuaki Matsubara, William Carlos Nahas, Franco Nolè, Eli Rosenbaum, Axel Heidenreich, Yoshiyuki Kakehi, Amily Zhang, Heiko Krissel, Michael Teufel, Junwu Shen, Volker Wagner, Celestia Higano
BACKGROUND: Abiraterone acetate plus prednisone or prednisolone improves progression-free survival and overall survival in patients with metastatic castration-resistant prostate cancer. Radium-223 improves overall survival and delays the onset of symptomatic skeletal events in patients with castration-resistant prostate cancer and bone metastases. We assessed concurrent treatment with abiraterone acetate plus prednisone or prednisolone and radium-223 in such patients. METHODS: We did a randomised, double-blind, placebo-controlled, phase 3 trial at 165 oncology and urology centres in 19 countries...
February 6, 2019: Lancet Oncology
Vivek Subbiah, Peter Meade Anderson, Kalevi Kairemo, Kenneth R Hess, Winston W Huh, Vinod Ravi, Najat C Daw, Neeta Somaiah, Joseph A Ludwig, Robert S Benjamin, Sant P Chawla, David S Hong, Funda Meric-Bernstam, Gregory Ravizzini, Eugenie S Kleinerman, Homer A Macapinlac, Eric M Rohren
PURPOSE: The prognosis of metastatic osteosarcoma continues to be poor. We hypothesized that alpha-emitting, bone-targeting radium 223 dichloride (223 RaCl2 ) can be safely administered to patients with osteosarcoma and that early signals of response or resistance can be assessed by quantitative and qualitative correlative imaging studies and biomarkers. EXPERIMENTAL DESIGN: A 3+3 phase I, dose-escalation trial of 223 RaCl2 (50, 75, and 100 kBq/kg) was designed in recurrent/metastatic osteosarcoma patients aged ≥15 years...
February 7, 2019: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Yadong Guo, Shiyu Mao, Aihong Zhang, Ruiliang Wang, Ziwei Zhang, Junfeng Zhang, Longsheng Wang, Wentao Zhang, Yuan Wu, Lin Ye, Bin Yang, Xudong Yao
Objective: This study compared the clinicopathological features and survival of metastatic prostate cancer (mPCa) after stratification by age and non-bone-related metastasis to identify prognostic factors. Methods: Patients with mPCa between 2010 and 2015 were identified from the Surveillance, Epidemiology and End Results database and analyzed. The overall survival (OS) rate was assessed using the Kaplan-Meier curve and log-rank test as well as multivariate Cox regression analysis. Results: Among the 10147 patients with mPCa, 5378 were classified as young (≤70 years), 3140 were classified as middle-aged (70-82 years), and 1629 were classified as elderly (> 82 years)...
2019: Journal of Cancer
Cong Zhang, Lei Yan, Hongkai Song, Zheng Ma, Dongshan Chen, Feilong Yang, Liang Fang, Zeyan Li, Kui Li, Dawei Li, Nengwang Yu, Hainan Liu, Zhonghua Xu
Objective: To evaluate the value of serum sialic acid (SA) in diagnosis of benign prostatic hyperplasia (BPH), prostate cancer (PCa), and bone metastases in PCa patients. Materials and Methods: Data from 540 patients who were newly diagnosed with PCa or BPH between November 2014 and March 2018 were retrospectively collected and analyzed. Pretreatment SA levels were compared across various groups, then, associations between SA levels and clinic parameters of patients were analyzed as well. Univariate and multivariate logistic regression analyses were further used to identify independent associations...
2019: Journal of Cancer
Ashutosh Dash, Tapas Das, F F Russ Knapp
Bone pain arising from secondary skeletal malignancy constitutes one of the most common types of chronic pain among patients with cancer which can lead to rapid deterioration in quality of life. Radionuclide therapy using bone-seeking radiopharmaceuticals based on the concept of localization of the agent at the bone metastases sites to deliver focal cytotoxic levels of radiation emerged as an effective treatment modality for the palliation of symptomatic bone metastases. Bone-seeking radiopharmaceuticals not only provide palliative benefit but also improve clinical outcomes in term of overall and progression-free survival...
February 1, 2019: Current Medicinal Chemistry
R Lozano, E Almagro, E Castro
Currently, there are several options available for the treatment of metastatic castration resistant prostate cancer (mCRPC), however evidence on the optimal treatment sequence is lacking. 223 Ra is the first targeted alpha therapy that has shown an improvement in overall survival in mCRPC patients. This drug specifically targets bone lesions, so there is a window of opportunity for the administration of 223 Ra previous to the development of visceral metastases. This should be taken into account to design the therapeutic strategy for mCRPC patients...
January 30, 2019: Revista Española de Medicina Nuclear e Imagen Molecular
Alberto Dalla Volta, Annamaria Formenti, Alfredo Berruti
Results from the ERA 223 trial of abiraterone combined with radium-223 among men with chemotherapy-naïve castration-resistant prostate cancer and bone metastases show no improvement in survival free from symptomatic skeletal events. We hypothesize that this finding might be attributable to bone loss induced by the concomitantly administered prednisone.
January 30, 2019: European Urology
A Larbi, P Omoumi, V Pasoglou, N Michoux, P Triqueneaux, B Tombal, C Cyteval, F E Lecouvet
PURPOSE: To assess the distribution of bone lesions in patients with prostate cancer (PCa) and those with multiple myeloma (MM) using whole-body magnetic resonance imaging (MRI); and to assess the added value of four anatomical regions located outside the thoraco-lumbo-pelvic area to detect the presence of bone lesions in a patient-based perspective. MATERIALS AND METHODS: Fifty patients (50 men; mean age, 67±10 [SD] years; range, 59-87 years) with PCa and forty-seven patients (27 women, 20 men; mean age, 62...
January 28, 2019: Diagnostic and Interventional Imaging
Stephanie A Harmon, Esther Mena, Joanna H Shih, Stephen Adler, Yolanda McKinney, Ethan Bergvall, Sherif Mehralivand, Adam G Sowalsky, Anna Couvillon, Ravi A Madan, James L Gulley, Janet Eary, Ronnie C Mease, Martin G Pomper, William L Dahut, Baris Turkbey, Liza Lindenberg, Peter L Choyke
Purpose: Prostate-Specific Membrane Antigen (PSMA) PET/CT has been introduced as a sensitive method for characterizing metastatic prostate cancer. The purpose of this study is to compare the spatial concordance of 18 F-NaF PET/CT and 18 F-PSMA-targeted PET/CT within prostate cancer bone metastases. Methods: Prostate cancer patients with known bone metastases underwent PSMA-targeted PET/CT (18 F-DCFBC or 18 F-DCFPyL) and 18 F-NaF PET/CT. In pelvic and spinal lesions detected by both radiotracers, regions-of-interest (ROIs) derived by various thresholds of uptake intensity were compared for spatial colocalization...
December 28, 2018: Oncotarget
Dominik Deniffel, Andreas Sauter, Julia Dangelmaier, Alexander Fingerle, Ernst J Rummeny, Daniela Pfeiffer
INTRODUCTION: To investigate the utility of quantitative dual-energy spectral CT derived iodine concentration (IC), in comparison with conventional CT attenuation, for the differentiation of pulmonary metastases from different primary malignancies. MATERIALS AND METHODS: CT scans were performed on a dual-layer spectral CT. We retrospectively evaluated pulmonary metastases of 130 patients (77 men and 53 women, mean age 63, range 22-87) with primary bone (OS) (osteosarcoma; n = 6), breast (invasive-ductal adenocarcinoma; n = 17), colorectal (CRC) (adenocarcinoma; n = 27), head and neck (HNC) (squamous cell carcinoma; n = 17), kidney (RCC) (clear-cell renal cell carcinoma; n = 10), lung (adenocarcinoma; n = 12), pancreato-biliary (PBC) (adenocarcinoma; n = 18), prostate (adenocarcinoma; n = 5), soft tissue (undifferentiated pleomorphic sarcoma; n = 6), skin (malignant melanoma; n = 6), and urinary tract (transitional-cell carcinoma; n = 6) malignancies...
February 2019: European Journal of Radiology
Jennifer L Beaumont, Zeeshan Butt, Rui Li, David Cella
BACKGROUND: The Functional Assessment of Cancer Therapy-Prostate (FACT-P) and the National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy-Prostate Symptom Index-17 (NFPSI-17) are 2 commonly used measures for patient-reported outcomes in prostate cancer trials. Their use may be enhanced by a better understanding of how change scores on the measures should be interpreted. METHODS: Using data from the phase 3 Alpharadin in Symptomatic Prostate Cancer Patients trial, this study estimated important change scores on the FACT-P and the NFPSI-17 via a combination of distribution- and anchor-based methods...
January 28, 2019: Cancer
Bo Chen, Homer A Macapinlac, Yang Lu
A 76-year-old man presented with recently diagnosed prostate adenocarcinoma, Gleason score of 4 + 4, and a Super bone scan with concurrent PSA of 1.7 ng/mL. Approximately 3.5 months later, an F-fluciclovine PET/CT was performed despite of a decreased PSA of 0.3 ng/mL. A Superscan fluciclovine PET/CT was identified, and bone metastasis were later confirmed at biopsy.
January 25, 2019: Clinical Nuclear Medicine
Thomas W Barber, Aviral Singh, Harshad R Kulkarni, Karin Niepsch, Baki Billah, Richard P Baum
177 Lu-labelled prostate-specific membrane antigen (PSMA) radioligand therapy using PSMA-617 and PSMA-I&T ligands (177 Lu-PRLT) is an emerging treatment in metastatic castration resistant prostate cancer (mCRPC). This retrospective study evaluates clinical outcomes of 177 Lu-PRLT in taxane chemotherapy pretreated (T-pretreated) and taxane chemotherapy naïve (T-naïve) patients with mCRPC. Materials and Methods: A retrospective analysis was performed on 167 patients with mCRPC who underwent 177 Lu-PRLT between March-2013 and December-2016...
January 25, 2019: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Samuli Arvola, Ivan Jambor, Anna Kuisma, Jukka Kemppainen, Sami Kajander, Marko Seppänen, Tommi Noponen
BACKGROUND: Despite recent technological advances allowing for quantitative single-photon emission computed tomography (SPECT), quantitative SPECT has not been widely used in the clinical practice. The aim of this study is to evaluate the feasibility of quantitative SPECT for measuring metastatic bone uptake in breast and prostate cancer by comparing standard uptake values (SUVs) measured with 99m Tc-HDP SPECT/CT and 18 F-NaF PET/CT. METHODS: Twenty-six breast and 27 prostate cancer patients at high risk of bone metastases underwent both 99m Tc-HDP SPECT/CT and 18 F-NaF PET/CT within 14 days of each other...
January 24, 2019: EJNMMI Research
Arsela Prelaj, Sara Elena Rebuzzi, Federica Buzzacchino, Chiara Pozzi, Carla Ferrara, Viviana Frantellizzi, Giulia Anna Follacchio, Liana Civitelli, Giuseppe De Vincentis, Silverio Tomao, Vincenzo Bianco
Radium-223 has improved overall survival (OS) and reduced symptomatic skeletal events (SSE) in patients with metastatic castration-resistant prostate cancer (mCRPC) and bone metastases (ALSYMPCA trial). Our aim was to assess clinical and biochemical factors related to survival, safety and survival outcomes of Radium-223 in a clinical practice setting. We retrospectively analysed 32 mCRPC patients treated with Radium-223, assessing bone scan, pain reduction, alkaline phosphatase (ALP) and prostate-specific antigen (PSA) response (≥30% reduction)...
February 2019: Oncology Letters
Ayelet Atkins, Mikhail Burke, Saeid Samiezadeh, Margarete K Akens, Michael Hardisty, Cari M Whyne
Metastasis of cancer to the spine impacts bone quality. This study aims to characterize vertebral microdamage secondary to metastatic disease considering the pattern of damage and its relationship to stress and strain under load. Osteolytic and mixed osteolytic/osteoblastic vertebral metastases were produced in athymic rats via HeLa cervical or canine Ace-1 prostate cancer cell inoculation, respectively. After 21 days, excised motion segments (T12-L2) were µCT scanned, stained with BaSO4 and re-imaged. T13-L2 motion segments were loaded in axial compression to induce microdamage, re-stained and re-imaged...
January 23, 2019: Annals of Biomedical Engineering
Peter A van Dam, Yannick Verhoeven, Xuan B Trinh, An Wouters, Filip Lardon, Hans Prenen, Evelien Smits, Marcella Baldewijns, Martin Lammens
Binding between the receptor activator of nuclear factor-kB (RANK) and its ligand (RANKL) triggers recruitment of TNF receptor associated factor (TRAF) adaptor proteins and activation of downstream pathways. RANK/RANKL signaling is controlled by a decoy receptor called osteoprotegerin (OPG) which interacts with RANKL. Additional networks regulating RANK/RANKL signaling are active in a context specific manner. RANK/RANKL signaling is essential for the differentiation of bone-resorbing osteoclasts, and is deregulated in pathological processes such as postmenopausal osteoporosis or cancer induced bone destruction...
January 2019: Critical Reviews in Oncology/hematology
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