scholarly journals A novel tool for improving the interpretation of isotope bone scans in metastatic prostate cancer

2020 ◽  
Vol 93 (1115) ◽  
pp. 20200775
Author(s):  
ALI H.D. Alshehri ◽  
Sarah O.S. Osman ◽  
Kevin M. Prise ◽  
Caoimhghin Campfield ◽  
PG Turner ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastases ◽  
Clinical Utility ◽  
Bone Scan ◽  
Metastatic Prostate Cancer ◽  
Imaging Modality ◽  
Skeletal Metastases ◽  
Bone Lesions ◽  
Subjective Interpretation ◽  
Radium 223

Objectives: The isotope bone scan (IBS) is the gold-standard imaging modality for detecting skeletal metastases as part of prostate cancer staging. However, its clinical utility for assessing skeletal metastatic burden is limited due to the need for subjective interpretation. We designed and tested a novel custom software tool, the Metastatic Bone Scan Tool (MetsBST), aimed at improving interpretation of IBSs, and compared its performance with that of an established software programme. Methods: We used IBS images from 62 patients diagnosed with prostate cancer and suspected bone metastases to design and implement MetsBST in MATLAB by defining thresholds used to identify the texture and size of metastatic bone lesions. The results of MetsBST were compared with those of the commercially available automated Bone Scan Index (aBSI) with regression analysis. Results: There was strong agreement between the MetsBST and aBSI results (R2 = 0.9189). In a subregional analysis, MetsBST quantified the extent of metastatic disease in multiple bone sites in patients receiving multimodality therapy (radium-223 and external beam radiotherapy) to illustrate the differences in bone metastatic response to different treatments. Conclusion: The results of MetsBST and the commercial software aBSI were highly consistent. MetsBST introduces novel clinical utility by its ability to differentiate between the responses of different bone metastases to multimodality therapies. Advances in knowledge: MetsBST reduces the variability in assessment of tumour burden caused by subjective interpretation. Therefore, it is a useful aid to physicians reporting nuclear medicine scans, and may improve decision-making in the treatment of metastatic prostate cancer.

scholarly journals Targeting the BMP Pathway in Prostate Cancer Induced Bone Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Desiree M. Straign ◽  
Claire L. Ihle ◽  
Meredith D. Provera ◽  
Philip Owens
Keyword(s):  
Prostate Cancer ◽  
Bone Metastasis ◽  
Bone Metastases ◽  
Bone Disease ◽  
Bone Health ◽  
Metastatic Prostate Cancer ◽  
Bone Lesions ◽  
Prostate Cell ◽  
Prostate Cell Line ◽  
Lytic Bone Lesions

From the 33,000 men in the U.S. who die from prostate cancer each year, the majority of these patients exhibit metastatic disease with bone being the most common site of metastasis. Prostate cancer bone metastases are commonly blastic, exhibiting new growth of unhealthy sclerotic bone, which can cause painful skeletal related events. Patient’s current care entails androgen deprivation therapy, anti-resorptive agents, radiation, and chemotherapy to help control the spread of the cancer but little intervention is available to treat blastic bone disease. The transforming growth factor beta (TGFβ) and bone morphogenetic protein (BMP) pathways are known to regulate bone growth and resorption of destructive lytic bone lesions, yet the role of TGFβ/BMP signaling in prostate cancer blastic vs lytic bone lesions are not fully understood. We hypothesized that to target the BMP/TGFβ pathway, a useful biomarker of bone lytic or blastic pathology would have superior response. We show distinct BMP vs. TGFβ signaling in clinical samples of human prostate cancer bone metastases with either lytic or blastic pathologies. BMPs exhibit distinct effects on bone homeostasis, so to examine the effect of BMP inhibition on healthy bone, we treated mice with the BMP receptor small molecule antagonist DMH1 and saw a modest temporary improvement in bone health, with increased trabecular bone. We next sought to use the BMP inhibitor DMH1 to treat bone metastasis engraftment seeded by a caudal artery injection of the lytic human prostate cell line PC3 in immunodeficient mice. The colonization by PC3 cells to the bone were restricted with DMH1 treatment and bone health was importantly preserved. We next proceeded to test BMP inhibition in an injury model of established bone metastasis via intratibial injection of the MYC-CaP mouse prostate cell line into FVBN syngeneic mice. DMH1 treated mice had a modest decrease in trabecular bone and reduced lymphocytes in circulation without affecting tumor growth. Taken together we show unique responses to BMP inhibition in metastatic prostate cancer in the bone. These studies suggest that profiling bone lesions in metastatic prostate cancer can help identify therapeutic targets that not only treat the metastatic tumor but also address the need to better treat the distinct tumor induced bone disease.

Alpha-Emitter Radium-223 in the Management of Solid Tumors: Current Status and Future Directions

2014 ◽  
pp. e132-e139 ◽  
Author(s):  
Sten Nilsson
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Bone Metastases ◽  
High Energy ◽  
Myelogenous Leukemia ◽  
Phase Iii ◽  
Current Status ◽  
Skeletal Metastases ◽  
Radium 223 ◽  
Alpha Emitter

Bone metastases, which are commonly seen in patients with advanced cancers, are a major cause of skeletal events, disability, and death. Radium-223 dichloride (radium-223; Xofigo, formerly Alpharadin), a first-in-class, alpha-emitting radiopharmaceutical that selectively targets bone metastases with high-energy short-range alpha-particles, has been approved for the treatment of patients with castration-resistant prostate cancer (CRPC) with symptomatic bone metastases and no known visceral metastases. Approval is based on results of the randomized phase III trial Alpharadin in Symptomatic Prostate Cancer (ALSYMPCA), in which radium-223 prolonged overall survival and time to first symptomatic skeletal event versus placebo among patients with CRPC with symptomatic bone metastases and was generally well tolerated, with low myelosuppression rates and manageable gastrointestinal adverse events. Long-term follow-up of the ALSYMPCA safety population showed that the incidence of myelosuppression remained low among patients treated with radium-223, with no additional safety issues of acute myelogenous leukemia, myelodysplastic syndrome, aplastic anemia, or primary bone cancer within approximately 1.5 years after treatment. The radium-223 overall survival benefit and low toxicity make it an effective, well-tolerated, and novel treatment option for CRPC and symptomatic bone metastases and opens the possibility of exploring radium-223 in the treatment of bone metastases from other cancers. A phase I clinical trial of patients with breast and prostate cancer with skeletal metastases demonstrated that radium-223 was safe and well tolerated at all therapeutically relevant dosages. Moreover, a phase IIa trial of patients with advanced breast cancer and progressive bone-dominant disease demonstrated that radium-223 targeted areas of increased bone metabolism and showed biologic activity.

scholarly journals Prostate Cancer Presenting with Parietal Bone Metastasis

2017 ◽  
Vol 2017 ◽  
pp. 1-3
Author(s):  
Brahima Kirakoya ◽  
Abdoul Karim Pare ◽  
Babagana Mustapha Abubakar ◽  
Moussa Kabore
Keyword(s):  
Prostate Cancer ◽  
Bone Metastasis ◽  
Bone Metastases ◽  
Metastatic Prostate Cancer ◽  
Axial Skeleton ◽  
Parietal Bone ◽  
Cranial Bone ◽  
Bone Lesions ◽  
Urological Symptoms ◽  
Left Parietal Bone

Bone metastases from prostate cancer are very common. They are usually located on the axial skeleton. However, cranial bone metastases especially to the parietal bone are rare. We report a case of metastatic prostate cancer presenting with left parietal bone metastasis in a patient with no urological symptoms or signs. We should consider prostate cancer in any man above 60 years presenting unusual bone lesions.

Clinical utility of Foundation One tissue molecular profiling in men with metastatic prostate cancer.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 318-318
Author(s):  
Jason Zhu ◽  
Matthew D Tucker ◽  
Patrick Healy ◽  
Michael Sandon Humeniuk ◽  
Casey Jarvis ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Utility ◽  
Metastatic Prostate Cancer ◽  
Parp Inhibitors ◽  
Cancer Center ◽  
Genomic Alterations ◽  
Pten Loss ◽  
Radium 223 ◽  
Clinical Benefits ◽  
Platinum Chemotherapy

318 Background: In the era of precision medicine, significant effort has been placed on identifying clinically actionable molecular targets to aid in the treatment of metastatic prostate cancer (mPC). Recent data supports homologous repair and mismatch repair deficiencies to guide the use of PARP inhibitors/platinum chemotherapy or pembrolizumab, respectively. We analyzed the clinical utility of Foundation One (FO) somatic genomic profiling in men with mPC. Methods: We performed a retrospective review of men with mPC in the Duke Cancer Center who received FO testing 01/2010 - 04/2017. We asked whether FO testing identified actionable genomic lesions that led to a change in clinical practice, and if men benefited from this novel genomic matched approach to treatment. Results: We identified 77 men with FO tests. Of these, 77% (59/77) had adequate tissue for FO testing. 76% had mCRPC, 42% had > 3 prior systemic therapies (enzalutamide 51%, docetaxel 39%, abiraterone 41%, sip-T 34%, radium-223 22%). The most common FO genomic alterations were: TP53 deletion/mutation (37%), TMPRSS2-ERG fusion (32%), and PTEN loss (31%). FO revealed 207 genomic alterations, classified into actionable (6), potentially actionable (44), non-actionable (126), and non-informative (31). Of the 6 patients with actionable mutations (BRCA2, ATM, PALB mutation/loss), 4 (67%) received matched olaparib therapy and 3 had PSA or prolonged radiographic stabilization, with durations of therapy of 3-19 months. Of 28 men with potentially actionable genomic findings, 3 (11%) received targeted therapies, including olaparib for a CDK12 mutation, and pembrolizumab for a PMS2 mutation and for a PD-L2 genomic gain. No responses to pembro were observed; the man with a CDK12 mutation responded to olaparib for 8 months. Overall, 42% (25/59) of evaluable men did not have a targetable mutation; 4/77 (5%) had clinical benefits from testing. Conclusions: A small but significant minority (~5%) of men with mPC appear to benefit from FO somatic tumor profiling, particularly those with homologous repair deficiencies. Larger prospective studies are needed with clinical outcomes in order to further understand the clinical utility of routine FO testing in this setting.

scholarly journals A novel DNA methylation signature is associated with androgen receptor activity and patient prognosis in bone metastatic prostate cancer

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Erik Bovinder Ylitalo ◽  
Elin Thysell ◽  
Mattias Landfors ◽  
Maria Brattsand ◽  
Emma Jernberg ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Androgen Receptor ◽  
Bone Metastases ◽  
Metastatic Prostate Cancer ◽  
Tumor Biology ◽  
Receptor Activity ◽  
Mrna Levels ◽  
Androgen Receptor Activity ◽  
Patient Prognosis

Abstract Background Patients with metastatic prostate cancer (PC) are treated with androgen deprivation therapy (ADT) that initially reduces metastasis growth, but after some time lethal castration-resistant PC (CRPC) develops. A better understanding of the tumor biology in bone metastases is needed to guide further treatment developments. Subgroups of PC bone metastases based on transcriptome profiling have been previously identified by our research team, and specifically, heterogeneities related to androgen receptor (AR) activity have been described. Epigenetic alterations during PC progression remain elusive and this study aims to explore promoter gene methylation signatures in relation to gene expression and tumor AR activity. Materials and methods Genome-wide promoter-associated CpG methylation signatures of a total of 94 tumor samples, including paired non-malignant and malignant primary tumor areas originating from radical prostatectomy samples (n = 12), and bone metastasis samples of separate patients with hormone-naive (n = 14), short-term castrated (n = 4) or CRPC (n = 52) disease were analyzed using the Infinium Methylation EPIC arrays, along with gene expression analysis by Illumina Bead Chip arrays (n = 90). AR activity was defined from expression levels of genes associated with canonical AR activity. Results Integrated epigenome and transcriptome analysis identified pronounced hypermethylation in malignant compared to non-malignant areas of localized prostate tumors. Metastases showed an overall hypomethylation in relation to primary PC, including CpGs in the AR promoter accompanied with induction of AR mRNA levels. We identified a Methylation Classifier for Androgen receptor activity (MCA) signature, which separated metastases into two clusters (MCA positive/negative) related to tumor characteristics and patient prognosis. The MCA positive metastases showed low methylation levels of genes associated with canonical AR signaling and patients had a more favorable prognosis after ADT. In contrast, MCA negative patients had low AR activity associated with hypermethylation of AR-associated genes, and a worse prognosis after ADT. Conclusions A promoter methylation signature classifies PC bone metastases into two groups and predicts tumor AR activity and patient prognosis after ADT. The explanation for the methylation diversities observed during PC progression and their biological and clinical relevance need further exploration.

scholarly journals Prostatic Acid Phosphatase Alters the RANKL/OPG System and Induces Osteoblastic Prostate Cancer Bone Metastases

Endocrinology ◽  
2016 ◽  
Vol 157 (12) ◽  
pp. 4526-4533 ◽  
Author(s):  
Alexander Kirschenbaum ◽  
Sudeh Izadmehr ◽  
Shen Yao ◽  
Kieley L. O’Connor-Chapman ◽  
Alan Huang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Acid Phosphatase ◽  
Bone Metastases ◽  
Cross Talk ◽  
Bone Cells ◽  
Bone Mineralization ◽  
Critical Role ◽  
Prostatic Acid Phosphatase ◽  
Bone Lesions ◽  
Rankl Expression

Prostate cancer (PCa) is unique in its tendency to produce osteoblastic (OB) bone metastases. There are no existing therapies that specifically target the OB phase that affects 90% of men with bone metastatic disease. Prostatic acid phosphatase (PAP) is secreted by PCa cells in OB metastases and increases OB growth, differentiation, and bone mineralization. The purpose of this study was to investigate whether PAP effects on OB bone metastases are mediated by autocrine and/or paracrine alterations in the receptor activator of nuclear factor κ-B (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system. To investigate whether PAP modulated these factors and altered the bone reaction, we knocked down PAP expression in VCaP cells and stably overexpressed PAP in PC3M cells, both derived from human PCa bone metastases. We show that knockdown of PAP in VCaP cells decreased OPG while increasing RANK/RANKL expression. Forced overexpression of PAP in PC3M cells had the inverse effect, increasing OPG while decreasing RANK/RANKL expression. Coculture of PCa cells with MC3T3 preosteoblasts also revealed a role for secretory PAP in OB-PCa cross talk. Reduced PAP expression in VCaP cells decreased MC3T3 proliferation and differentiation and reduced their OPG expression. PAP overexpression in PC3M cells altered the bone phenotype creating OB rather than osteolytic lesions in vivo using an intratibial model. These findings demonstrate that PAP secreted by PCa cells in OB bone metastases increases OPG and plays a critical role in the vicious cross talk between cancer and bone cells. These data suggest that inhibition of secretory PAP may be an effective strategy for PCa OB bone lesions.

Surgical treatment as option in treatment of metastatic hormone-sensitive prostate cancer after prior drug treatment

2022 ◽  
pp. 41-45
Author(s):  
Sh. G. Khakimova ◽  
G. G. Khakimova ◽  
G. A. Khakimov ◽  
J. B. Sadullaev
Keyword(s):  
Prostate Cancer ◽  
Surgical Treatment ◽  
Drug Treatment ◽  
Bone Metastases ◽  
Clinical Result ◽  
Metastatic Prostate Cancer ◽  
Clinical Case ◽  
Complex Treatment ◽  
Good Clinical Result ◽  
Hormone Sensitive

Currently, there is no consensus on the place of prostatectomy in the complex treatment of patients with metastatic prostate cancer. A description of a clinical case of complex treatment and observation of a patient with prostate cancer with an unfavorable baseline prognosis and the presence of bone metastases with a good clinical result is presented.

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