Alkaline Phosphatase in Metastatic Castration-Resistant Prostate Cancer: Reassessment of an Older Biomarker

Heinrich, Daniel; Bruland, Øyvind S.; Guise, Theresa A.; Suzuki, Hiroyoshi; Sartor, Oliver

doi:10.2217/fon-2018-0087

Cited by 54 publications

(44 citation statements)

References 94 publications

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“…Data coming from literature have shown that baseline tALP level is prognostic for OS. 28 Anyway, an increased risk of death, time to progression, skeletal-related events, and bone marrow failure are possibly related to pre-treatment tALP levels (≥146 U/L): this admits to hypothesize a predicting role for this marker. 29 In addition to that, from a retrospective analysis of data from the ALSYMPCA trial emerged that patients treated with Ra-223 and with confirmed decline in tALP at week 12 had a significantly longer OS.…”

Section: Discussionmentioning

confidence: 99%

Scintigraphic load of bone disease evaluated by DASciS software as a survival predictor in metastatic castration-resistant prostate cancer patients candidates to 223RaCl treatment

Frantellizzi

Pani

Ippoliti

et al. 2019

Radiology and Oncology

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BackgroundAim of our study was to assess the load of bone disease at starting and during Ra-223 treatment as an overall survival (OS) predictor in metastatic castration-resistant prostate cancer (mCRPC) patients. Bone scan index (BSI) is defined as the percentage of total amount of bone metastasis on whole-body scintigraphic images. We present a specific software (DASciS) developed by an engineering team of “Sapienza” University of Rome for BSI calculation.Patients and methods127 mCRPC patients bone scan images were processed with DASciS software, and BSI was tested as OS predictor.Results546 bone scans were analyzed revealing that the extension of disease is a predictor of OS (0–3% = 28 months of median survival (MoMS]; 3%–5% = 11 MoMS, > 5% = 5 MoMS). BSI has been analyzed as a single parameter for OS, determining an 88% AUC. Moreover, the composition between the BSI and the 3-PS (3-variable prognostic score) determines a remarkable improvement of the AUC (91%), defining these two parameters as the best OS predictors.ConclusionsThis study suggests that OS is inversely correlated with the load of bone disease in mCRPC Ra-223-treated subjects. DASciS software appears a promising tool in identifying mCRPC patients that more likely take advantage from Ra-223 treatment. BSI is proposed as a predictive variable for OS and included to a multidimensional clinical evaluation permits to approach the patients’ enrollment in a rational way, allowing to enhance the treatment effectiveness together with cost optimization.

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Section: Discussionmentioning

confidence: 99%

Scintigraphic load of bone disease evaluated by DASciS software as a survival predictor in metastatic castration-resistant prostate cancer patients candidates to 223RaCl treatment

Frantellizzi

Pani

Ippoliti

et al. 2019

Radiology and Oncology

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“…Since 90% of the mCRPC patients have radiologic evidence of bone metastasis [3], alkaline phosphatase is an important biomarker in prostate cancer. For cabazitaxel, no direct effect on alkaline phosphatase is known, only indirect when the tumor burden decreases, alkaline phosphatase levels also decrease [19]. Also for hemoglobin no direct effect of cabazitaxel is known.…”

Section: Discussionmentioning

confidence: 99%

Circulating Tumor Cell Enumeration and Characterization in Metastatic Castration-Resistant Prostate Cancer Patients Treated with Cabazitaxel

Kruijff

Sieuwerts

Onstenk

et al. 2019

Cancers

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(1) Background: Markers identifying which patients with metastatic, castration-resistant prostate cancer (mCRPC) will benefit from cabazitaxel therapy are currently lacking. Therefore, the aim of this study was to identify markers associated with outcome to cabazitaxel therapy based on counts and gene expression profiles of circulating tumor cells (CTCs). (2) Methods: From 120 mCRPC patients, CellSearch enriched CTCs were obtained at baseline and after 6 weeks of cabazitaxel therapy. Furthermore, 91 genes associated with prostate cancer were measured in mRNA of these CTCs. (3) Results: In 114 mCRPC patients with an evaluable CTC count, the CTC count was independently associated with poor progression-free survival (PFS) and overall survival (OS) in multivariable analysis with other commonly used variables associated with outcome in mCRPC (age, prostate specific antigen (PSA), alkaline phosphatase, lactate dehydrogenase (LDH), albumin, hemoglobin), together with alkaline phosphatase and hemoglobin. A five-gene expression profile was generated to predict for outcome to cabazitaxel therapy. However, even though this signature was associated with OS in univariate analysis, this was not the case in the multivariate analysis for OS nor for PFS. (4) Conclusion: The established five-gene expression profile in CTCs was not independently associated with PFS nor OS. However, along with alkaline phosphatase and hemoglobin, CTC-count is independently associated with PFS and OS in mCRPC patients who are treated with cabazitaxel.

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“…Differentiation of hMSCs to osteoblastic lineages in vitro is associated with their ability to express Col I and ALP. Col I is expressed by osteoblasts during the initial period of proliferation and ECM synthesis, while ALP is expressed during the post proliferative period of matrix maturation [260,261,262,263]. Osteogenic differentiation of hMSCs in vitro is greatly enhanced by DEXA.…”

Section: In Vitro Studiesmentioning

confidence: 99%

Synthetic Biodegradable Aliphatic Polyester Nanocomposites Reinforced with Nanohydroxyapatite and/or Graphene Oxide for Bone Tissue Engineering Applications

Liao

Tjong

2019

Nanomaterials

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This paper provides review updates on the current development of bionanocomposites with polymeric matrices consisting of synthetic biodegradable aliphatic polyesters reinforced with nanohydroxyaptite (nHA) and/or graphene oxide (GO) nanofillers for bone tissue engineering applications. Biodegradable aliphatic polyesters include poly(lactic acid) (PLA), polycaprolactone (PCL) and copolymers of PLA-PGA (PLGA). Those bionanocomposites have been explored for making 3D porous scaffolds for the repair of bone defects since nHA and GO enhance their bioactivity and biocompatibility by promoting biomineralization, bone cell adhesion, proliferation and differentiation, thus facilitating new bone tissue formation upon implantation. The incorporation of nHA or GO into aliphatic polyester scaffolds also improves their mechanical strength greatly, especially hybrid GO/nHA nanofilllers. Those mechanically strong nanocomposite scaffolds can support and promote cell attachment for tissue growth. Porous scaffolds fabricated from conventional porogen leaching, and thermally induced phase separation have many drawbacks inducing the use of organic solvents, poor control of pore shape and pore interconnectivity, while electrospinning mats exhibit small pores that limit cell infiltration and tissue ingrowth. Recent advancement of 3D additive manufacturing allows the production of aliphatic polyester nanocomposite scaffolds with precisely controlled pore geometries and large pores for the cell attachment, growth, and differentiation in vitro, and the new bone formation in vivo.

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Alkaline Phosphatase in Metastatic Castration-Resistant Prostate Cancer: Reassessment of an Older Biomarker

Cited by 54 publications

References 94 publications

Scintigraphic load of bone disease evaluated by DASciS software as a survival predictor in metastatic castration-resistant prostate cancer patients candidates to 223RaCl treatment

Scintigraphic load of bone disease evaluated by DASciS software as a survival predictor in metastatic castration-resistant prostate cancer patients candidates to 223RaCl treatment

Circulating Tumor Cell Enumeration and Characterization in Metastatic Castration-Resistant Prostate Cancer Patients Treated with Cabazitaxel

Synthetic Biodegradable Aliphatic Polyester Nanocomposites Reinforced with Nanohydroxyapatite and/or Graphene Oxide for Bone Tissue Engineering Applications

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