scholarly journals Objective criteria for MRI evaluation of the effectiveness of treatment of bone metastases in patients with prostate cancer and breast cancer: systematic review and meta-analysis

2021 ◽  
Author(s):  
Vladislav Olegovich Ripp ◽  
Tatyana Pavlovna Berezovskaya ◽  
Sergey Anatolyevich Ivanov
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Bone Metastases ◽  
Treatment Efficacy ◽  
High Efficiency ◽  
Bone Lesions ◽  
Cochrane Central Register ◽  
Quantitative Parameters ◽  
Mri Evaluation ◽  
Skeletal Lesions

Objectives. The possibility of a personalized approach to the treatment of metastatic prostate cancer and breast cancer requires objective methods for evaluation of response of foci treatment in the skeleton. The proven high efficiency of MRI in detecting bone metastases, in combination with the absence of ionizing radiation, has laid the groundwork for using this method in monitoring the treatment course based on objective criteria for evaluation of the therapeutic outcome. Aim. To analyze quantitative and semi-quantitative parameters of MRI-evaluation of treatment efficacy (radiation, chemotherapy, hormone therapy, and targeted therapy) of bone metastases that were used in prostate and breast cancer clinical trials. Materials and methods. The databases Embase, PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), eLibrary were searched until April 1, 2021, using the following keywords: magnetic resonance imaging, MRI, DWI, treatment response, prostate cancer or breast cancer, and bone metastasis. Only studies related to the MRI-evaluation of treatment efficacy of any type of therapeutic intervention (with the exception of surgery) for metastatic skeletal lesions have been included in this review. Results. Of the 312 sources found as a result of the search, 11 studies were selected and analyzed. It allowed us to identify four groups of objective MRI-criteria for evaluating the therapeutic effect in metastatic bone lesions in patients with prostate and breast cancer that include the dynamics of: a) sizes; b) signal intensity on DWI; c) ADC; d) tumor total diffusion volume (tDV). Changes in these quantitative and semi-quantitative indicators, with only one exception, had the same direction, although they differed in numerical values. Conclusion. MRI is an informative technique for the objective evaluation of the response of bone metastases to therapy in patients with prostate cancer and breast cancer based on quantitative and semi-quantitative parameters. It has significant potential as a diagnostic test instrument for monitoring the effectiveness of treatment of metastatic skeletal lesions.

Effect of the number of bone lesions on efficacy of zoledronic acid for prevention of skeletal-related events (SREs) in patients with bone metastases from solid tumors

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 8529-8529 ◽  
Author(s):  
N. Shirina ◽  
R. E. Coleman ◽  
Y. M. Chen
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Lung Cancer ◽  
Zoledronic Acid ◽  
Bone Metastases ◽  
Cancer Patients ◽  
Solid Tumors ◽  
Morbidity Rate ◽  
Bone Lesions ◽  
The Mean

8529 Background: It has been postulated that greater numbers of bone metastases and thus greater tumor burden may lead to increased skeletal morbidity. To assess the effect that the number of baseline bone metastases may have on the efficacy of zoledronic acid in patients with solid tumors, we conducted a retrospective analysis of 3 large, randomized, controlled trials. Methods: Data were evaluated from the intent-to-treat population with breast cancer (n = 739), prostate cancer (n = 397), or lung cancer and other solid tumors (n = 480) who were treated with zoledronic acid 4 mg, pamidronate 90 mg, or placebo and had information available on number of baseline bone lesions. Patients were stratified into 2 groups: those with ≤ 3 bone lesions or > 3 lesions. Results: In general, patients with > 3 lesions had a higher skeletal morbidity rate (SMR) compared with patients with ≤ 3 lesions (Table 1), and zoledronic acid reduced SREs regardless of the number of bone lesions, but the benefit of zoledronic acid appeared greater in patients with > 3 lesions. In patients with lung cancer and other solid tumors who had > 3 bone lesions, zoledronic acid significantly reduced the mean SMR (P = .008) and significantly prolonged time to first SRE (median, 171 vs 84 day; P = .005) compared with placebo. In prostate cancer patients with > 3 bone lesions, zoledronic acid also significantly reduced the mean SMR compared with placebo (Table 1). In breast cancer patients with > 3 bone lesions, the mean SMRs were similar for zoledronic acid and pamidronate groups (Table 1). Conclusions: Patients with a greater number of bone lesions are at higher risk for skeletal complications and receive greater clinical benefit from treatment with zoledronic acid. [Table: see text] [Table: see text]

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.

Breast cancer patients have better outcomes than prostate cancer patients for palliation of painful bone metastases: Results of RTOG 97–14

2005 ◽  
Vol 23 (16_suppl) ◽  
pp. 6073-6073
Author(s):  
W. F. Hartsell ◽  
K. Winter ◽  
D. W. Bruner ◽  
C. W. Scarantino ◽  
R. Ivker ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Bone Metastases ◽  
Cancer Patients ◽  
Breast Cancer Patients ◽  
Painful Bone Metastases

Measurement of DKK1 and FRP in breast and prostate cancer patients with bone metastases: Impact of zoledronic acid (ZA)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 19659-19659
Author(s):  
T. Helsten ◽  
M. Corr ◽  
J. E. Mortimer
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Bone Metastases ◽  
Cancer Patients ◽  
Post Treatment ◽  
Bone Homeostasis ◽  
Breast Cancer Patients ◽  
Bone Specific Alkaline Phosphatase ◽  
Osteoblast Activity ◽  
Breast And Prostate Cancer

19659 Background: Bone metastases produce an imbalance in osteoblast and osteoclast activity. While metastases from prostate cancer are osteoblastic, metastases from breast cancer may be osteolytic, osteoblastic or mixed. The wnt/frizzled pathway is involved in maturation of osteoblasts and in adult bone homeostasis. We explored the wnt antagonists dickkopf (DKK1) and frizzled related protein (FRP) as potential biomarkers in bone metastasis after ZA treatment. Methods: This is a pilot cohort study in bisphosphonate naive breast and prostate cancer patients with bone metastases. Cancer therapy was not specified. Patients received 2 monthly doses of ZA 4 mg IV. Pre- and post-treatment (day 60) sera were collected for measurement of FRP and DKK1, along with IL-6, calcium, creatinine and bone-specific alkaline phosphatase (BAP, a marker of osteoblast activity). Primary endpoint: mean change in FRP and DKK1; Secondary endpoints: correlation of biomarkers with each other and comparison of breast vs. prostate cancer patients. Biomarkers were measured using standard ELISA assays. Statistics: comparison of means = student t-test, correlation coefficients = Pearson. Results: Mature data from 14 patients are reported here, 9 with breast and 5 with prostate cancer. Mean age = 61 years (range 42–89). Two breast cancer patients were premenopausal. One prostate and 3 breast cancer patients received chemotherapy; all others were treated hormonally. After ZA, calcium decreased in all patients (p = 0.09). BAP decreased in all but 1 breast and 1 prostate cancer patient (mean decrease 20.0, p = 0.16). IL-6 was undetectable in most patients. FRP decreased in all but 4 patients (mean decrease 6.2, p = 0.13). There was no discernable pattern for DKK1. Pre-treatment DKK1 correlated with FRP (p = 0.01, r2 = 0.39), but there was no correlation post-treatment. Post-treatment DKK1 correlated with both serum calcium (p = 0.04, r2 = 0.49) and BAP (p = 0.005, r2 = 0.65). There was no difference between breast and prostate cancer patients. Conclusions: It is feasible to measure DKK1 and FRP in patients with malignant bone disease. Treatment with ZA has measurable effects upon these and other serum markers. Further studies with more patients are needed to evaluate their potential as biomarkers. No significant financial relationships to disclose.

Tartrate-resistant acid phosphatase as a marker of bone metastases in patients with breast cancer and prostate cancer

2004 ◽  
Vol 138 (7) ◽  
pp. 77-79 ◽  
Author(s):  
N. V. Lyubimova ◽  
M. V. Pashkov ◽  
S. A. Tyulyandin ◽  
V. E. Gol’dberg ◽  
N. E. Kushlinskii
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Acid Phosphatase ◽  
Bone Metastases ◽  
Tartrate Resistant Acid Phosphatase

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.

scholarly journals Correcting B0 inhomogeneity-induced distortions in whole-body diffusion MRI of bone metastases

2020 ◽  
Author(s):  
Leonardino A. Digma ◽  
Christine H. Feng ◽  
Christopher C. Conlin ◽  
Ana E. Rodríguez-Soto ◽  
Kanha Batra ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastases ◽  
Bone Lesion ◽  
Distortion Correction ◽  
Whole Body ◽  
Bone Lesions ◽  
Thoracic Vertebrae ◽  
Signed Rank ◽  
Spatial Displacements ◽  
T2 Weighted Images

AbstractBackgroundAccurate imaging of bone metastases is necessary for treatment planning and assessing treatment response. Diffusion-weighted magnetic resonance imaging (DWI) can detect bone metastases, but DWI acquired with echo-planar imaging is susceptible to distortions due to static magnetic field inhomogeneities.PurposeEstimate spatial displacements of bone lesions on DWI. Examine whether distortion-corrected DWI more accurately reflects underlying anatomy.Study TypeRetrospective.Subjects18 patients with prostate cancer bone metastases.Field Strength/Sequence3.0 T; DWI and T2-weighted imaging.AssessmentWe first applied the reverse polarity gradient (RPG) technique to estimate spatial displacements of bone metastasis on DWI. Next, we calculated changes in mutual information (MI) between DWI and T2-weighted images after RPG distortion correction. Further, we annotated skeletal landmarks on DWI and T2-weighted images. RPG was again used to estimate displacements of these landmarks. Lastly, we calculated changes in distance between DWI- and T2-defined landmarks (i.e., changes in error) after RPG distortion correction.Statistical TestsMean and bootstrap-derived confidence intervals were used to summarize variables that estimate bone lesion distortions. Wilcoxon signed-rank tests were used to assess change in MI between DWI and T2-weighted images after RPG.ResultsMean (95% CI) displacement of bone lesions was 5.6 mm (95% CI: 4.8-6.5); maximum displacement was 17.1 mm. Corrected diffusion images were more similar to structural MRI, as evidenced by consistent increases in MI after applying RPG (Wilcoxon signed-rank p<10−13). Like bone metastases, our annotated skeletal landmarks also underwent substantial displacement (average, 6.3 mm). Lastly, RPG led to consistent error reductions between DWI and T2 for each skeletal landmark (mean, [95% CI]): thoracic vertebrae (−3.8 mm, [-4.3,-3.3]), abdominal vertebrae (−1.0 mm, [-1.2,-0.71]), pelvic vertebrae (−0.6 mm, [-1.0,-0.17]), and femoral head (−1.2 mm, [-2.1,-0.4]).Data ConclusionsThese findings support the use of distortion correction techniques to improve localization of bone metastases on DWI.Grant SupportThis work was supported by NIH/NIBIB #K08EB026503, American Society for Radiation Oncology, and the Prostate Cancer Foundation. This work was further supported by the National Institute on Aging T35 grant AG26757 (PI: Dilip V. Jeste, MD, and Alison Moore, MD, MPH), and the Stein Institute for Research on Aging and the Center for Healthy Aging at the University of California, San Diego.

scholarly journals Castration Determines the Efficacy of ETAR Blockade in a Mouse Model of Prostate Cancer Bone Metastasis

Endocrinology ◽  
2019 ◽  
Vol 160 (8) ◽  
pp. 1786-1796
Author(s):  
Henry H Moon ◽  
Katrina L Clines ◽  
Mark A Cooks ◽  
Charlotte A Cialek ◽  
Marian A Esvelt ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastasis ◽  
Mouse Model ◽  
Advanced Prostate Cancer ◽  
Cancer Cell Line ◽  
Prostate Cancer Cell Line ◽  
Androgen Deprivation ◽  
Bone Lesions ◽  
Castration Resistant Prostate Cancer ◽  
Skeletal Lesions

Abstract Bone metastasis is a painful complication of advanced prostate cancer. Endothelin-1 is a tumor-secreted factor that plays a central role in osteoblast activation and the osteosclerotic response of prostate cancer metastatic to bone. Antagonists that block the activation of the endothelin A receptor (ETAR), located on osteoblasts, reduce osteoblastic bone lesions in animal models of bone metastasis. However, ETAR antagonists demonstrated limited efficacy in clinical trials of men with advanced prostate cancer who also received standard androgen deprivation therapy (ADT). Previous data from our group suggested that, in a mouse model, ETAR antagonists might only be efficacious when androgen signaling in the osteoblast is lowered beyond the ability of standard ADT. This notion was tested in a mouse model of prostate cancer bone metastasis. Castrated and sham-operated male athymic nude mice underwent intracardiac inoculation of the ARCaPM castration-resistant prostate cancer cell line. The mice were then treated with either the ETAR antagonist zibotentan or a vehicle control to generate four experimental groups: vehicle+sham (Veh+Sham), vehicle+castrate (Veh+Castr), zibotentan+sham (Zibo+Sham), and zibotentan+castrate (Zibo+Castr). The mice were monitored radiographically for the development of skeletal lesions. The Zibo+Castr group had significantly longer survival and a single incidental lesion. Mice in the Zibo+Sham group had the shortest survival and the largest number of skeletal lesions. Survival and skeletal lesions of the Veh+Sham and Veh+Castr groups were intermediate compared with the zibotentan-treated groups. We report a complex interaction between ETAR and androgen signaling, whereby ETAR blockade was most efficacious when combined with complete androgen deprivation.

scholarly journals Metastatic Bone Disease in Patients with Solid Tumors–-Burden of Bone Disease and the Role of Zoledronic Acid

2009 ◽  
Vol 1 ◽  
pp. CMT.S1958
Author(s):  
Vera Hirsh
Keyword(s):  
Breast Cancer ◽  
Zoledronic Acid ◽  
Bone Metastases ◽  
Bone Disease ◽  
Large Scale ◽  
Comparative Trial ◽  
Palliative Radiotherapy ◽  
Bone Lesions ◽  
Pathologic Fractures

Bisphosphonates have become an integral component of the therapeutic repertoire for cancer patients at risk for skeletal-related events (SREs) such as pathologic fractures, bone pain requiring palliative radiotherapy, the need for orthopedic surgery, spinal cord compression, and hypercalcemia of malignancy because of bone metastases. Administered via monthly 15-minute infusion of up to 4 mg (depending on creatinine clearance rate), zoledronic acid (ZOL) has been approved for preventing SREs in patients with bone metastases from any solid tumor or bone lesions from multiple myeloma. Although there have been limited head-to-head comparison trials between bisphosphonates, ZOL displayed benefits beyond pamidronate in a large-scale comparative trial in patients with bone metastases from breast cancer. Monitoring of serum creatinine levels and oral health is important to ensure safety and comfort during treatment. In addition to the established benefits of bisphosphonates in the advanced cancer setting, there is a strong preclinical rationale and emerging clinical evidence that ZOL has antitumor activities and can delay metastasis in patients with early breast cancer. Studies are underway in patients with other tumor types, and the role of bisphosphonates is likely to evolve.

Activity of cabozantinib (XL184) in metastatic breast cancer (MBC): Results from a phase II randomized discontinuation trial (RDT).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 535-535 ◽  
Author(s):  
Eric P. Winer ◽  
Sara Tolaney ◽  
Hovav Nechushtan ◽  
Raanan Berger ◽  
Razelle Kurzrock ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Metastases ◽  
Bone Scan ◽  
Tumor Regression ◽  
Objective Response ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Bone Lesions ◽  
Respiratory Compromise ◽  
Open Label

535 Background: Dysregulation of MET and VEGF signaling has been implicated in breast cancer development and progression, including tumor invasion and dissemination. Cabozantinib (cabo) is an oral, potent inhibitor of MET and VEGFR2. A RDT evaluated activity and safety in 9 tumor types, including MBC. Methods: Eligible patients (pts) were required to have progressive measurable disease per RECIST. Pts received cabo at 100 mg qd over a 12 wk Lead-in stage. Tumor response (mRECIST) was assessed q6 wks. Treatment ≥ wk 12 was based on response: pts with PR continued open-label cabo, pts with SD were randomized to cabo vs placebo, and pts with PD discontinued. Primary endpoint in the randomized discontinuation phase was progression-free survival (PFS). Results: Enrollment to this cohort is complete (n = 45); all pts are unblinded. Baseline characteristics: median age 56; invasive ductal 86%, invasive lobular 7%; ER+ 93%, HER2+ 18%, triple- 5%; visceral disease 91%; bone metastases 73%; median prior lines of therapy 3 (range 1-8), including 71% with prior anthracyclines. Median follow-up was 2.9 mos (range 0.1 -16). 21 pts (47%) completed Lead-in stage with only 9 randomized to continue cabo (n = 5) or placebo (n = 4). Median PFS from Study Day 1 was 4.1 mos. At wk 12, objective response rate was 14% and disease control rate 48%. Tumor regression was observed in 25/39 pts (64%) with ≥1 post-baseline tumor assessment. 4/10 pts evaluable by bone scan had partial resolution of bone lesions. Of 12 pts receiving narcotics for bone pain, 5 pts reported improved pain and 2 pts had decreased narcotics use, per investigator. 4/14 evaluable pts (29%) with bone metastases experienced ≥50% decline in serum NTx. Most common Grade 3/4 AEs were palmar-plantar erythrodyesthesia (13%) and fatigue (11%). One related Grade 5 AE of respiratory compromise was reported during the Lead-in stage. Conclusions: Cabo demonstrated a 14% rate of objective tumor regression in heavily pretreated MBC pts. Observed effects on bone scan and pain are consistent with those seen in other malignancies. The safety profile of cabo was comparable to that seen with other VEGFR TKIs.

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