The histopathology of skeletal metastases

Whole-body scintigraphy with both 99mTc-phosphonate and 67Ga was performed on 92 patients suspected of primary bone tumors. In 46 patients with primary malignant bone tumors, scintigraphy with 99mTc-phosphonate disclosed the primary tumor in 44 cases and skeletal metastases in 11, and 67Ga scintigraphy detected the primary tumor in 43 cases, skeletal metastases in 6 cases and soft-tissue metastases in 8 cases. In 25 patients with secondary malignant bone tumors, bone scintigraphy visualized a single lesion in 10 cases and several lesions in 15 cases, and 67Ga scintigraphy detected the primary tumor in 17 cases, skeletal metastases in 17 cases and soft-tissue metastases in 9 cases. In 21 patients with benign bone disease positive uptake of 99mTc-phosphonate was recognized in 19 cases and uptake of 67Ga in 17 cases. It is concluded that bone scintigraphy should be used in patients suspected of primary bone tumors. If malignancy is suspected, 67Ga scintigraphy should be performed in addition.

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Computed Tomography of Skeletal Metastases with Contrast

10.32388/qq7q58 ◽

2020 ◽

Author(s):

Keyword(s):

Computed Tomography ◽

Skeletal Metastases

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HGK promotes metastatic dissemination in prostate cancer

Scientific Reports ◽

10.1038/s41598-021-91292-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Sara Garcia-Garcia ◽

Maria Rodrigo-Faus ◽

Noelia Fonseca ◽

Sara Manzano ◽

Balázs Győrffy ◽

...

Keyword(s):

Prostate Cancer ◽

Prognostic Biomarker ◽

Skeletal Metastases ◽

Primary Tumors ◽

Prostate Tumorigenesis ◽

Actin Organization ◽

Multi Stage ◽

Adhesion Stability ◽

Therapeutic Alternatives ◽

Cell Dissemination

AbstractMetastasis is the process of cancer cell dissemination from primary tumors to different organs being the bone the preferred site for metastatic homing of prostate cancer (PCa) cells. Prostate tumorigenesis is a multi-stage process that ultimately tends to advance to become metastatic PCa. Once PCa patients develop skeletal metastases, they eventually succumb to the disease. Therefore, it is imperative to identify essential molecular drivers of this process to develop new therapeutic alternatives for the treatment of this devastating disease. Here, we have identified MAP4K4 as a relevant gene for metastasis in PCa. Our work shows that genetic deletion of MAP4K4 or pharmacological inhibition of its encoded kinase, HGK, inhibits metastatic PCa cells migration and clonogenic properties. Hence, MAP4K4 might promote metastasis and tumor growth. Mechanistically, our results indicate that HGK depleted cells exhibit profound differences in F-actin organization, increasing cell spreading and focal adhesion stability. Additionally, HGK depleted cells fails to respond to TNF-α stimulation and chemoattractant action. Moreover, here we show that HGK upregulation in PCa samples from TCGA and other databases correlates with a poor prognosis of the disease. Hence, we suggest that it could be used as prognostic biomarker to predict the appearance of an aggressive phenotype of PCa tumors and ultimately, the appearance of metastasis. In summary, our results highlight an essential role for HGK in the dissemination of PCa cells and its potential use as prognostic biomarker.

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An international expert opinion statement on the utility of PET/MR for imaging of skeletal metastases

European Journal of Nuclear Medicine and Molecular Imaging ◽

10.1007/s00259-021-05198-2 ◽

2021 ◽

Author(s):

Jad S. Husseini ◽

Bárbara Juarez Amorim ◽

Angel Torrado-Carvajal ◽

Vinay Prabhu ◽

David Groshar ◽

...

Keyword(s):

Expert Opinion ◽

Skeletal Metastases ◽

International Expert

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[177Lu]Lu-DOTA-ZOL bone pain palliation in patients with skeletal metastases from various cancers: efficacy and safety results

EJNMMI Research ◽

10.1186/s13550-020-00709-y ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Madhav Prasad Yadav ◽

Sanjana Ballal ◽

Marian Meckel ◽

Frank Roesch ◽

Chandrasekhar Bal

Keyword(s):

Overall Survival ◽

Pain Assessment ◽

Bone Pain ◽

Performance Status ◽

Response Assessment ◽

Assessment Criteria ◽

Skeletal Metastases ◽

Efficacy And Safety ◽

Pain Palliation ◽

Global Pain

Abstract Background [177Lu]Lu-DOTA-ZOL has shown promising results from the dosimetry and preclinical aspects, but data on its role in the clinical efficacy are limited. The objective of this study is to evaluate the efficacy and safety of [177Lu]Lu-DOTA-ZOL as a bone pain palliation agent in patients experiencing pain due to skeletal metastases from various cancers. Methods In total, 40 patients experiencing bone pain due to skeletal metastases were enrolled in this study. The patients were treated with a mean cumulative dose of 2.1 ± 0.6 GBq (1.3–2.7 GBq) [177Lu]Lu-DOTA-ZOL in a median follow-up duration of 10 months (IQR 8–14 months). The primary outcome endpoint was response assessment according to the visual analogue score (VAS). Secondary endpoints included analgesic score (AS), global pain assessment score, Eastern Cooperative Oncology Group Assessment performance status (ECOG), Karnofsky performance status, overall survival, and safety assessment by the National Cancer Institute’s Common Toxicity Criteria V5.0. Results In total, 40 patients (15 males and 25 females) with a mean age of 46.6 ± 15.08 years (range 24–78 years) were treated with either 1 (N = 15) or 2 (N = 25) cycles of [177Lu]Lu-DOTA-ZOL. According to the VAS response assessment criteria, complete, partial, and minimal responses were observed in 11 (27.5%), 20 (50%), and 5 patients (12.5%), respectively with an overall response rate of 90%. Global pain assessment criteria revealed complete, partial, minimal, and no response in 2 (5%), 25 (62.5%), 9 (22.5%), and 4 (10%) patients, respectively. Twenty-eight patients died and the estimated median overall survival was 13 months (95% CI 10–14 months). A significant improvement was observed in the VAS, AS, and ECOG status when compared to baseline. None of the patients experienced grade III/IV haematological, kidney, or hepatotoxicity due to [177Lu]Lu-DOTA-ZOL therapy. Conclusion [177Lu]Lu-DOTA-ZOL shows promising results and is an effective radiopharmaceutical in the treatment of bone pain due to skeletal metastases from various cancers.

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A Retrospective Comparative Study of Sodium Fluoride (NaF-18)-PET/CT and Fluorocholine (F-18-CH) PET/CT in the Evaluation of Skeletal Metastases in Metastatic Prostate Cancer Using a Volumetric 3-D Radiomics Analysis

Diagnostics ◽

10.3390/diagnostics11010017 ◽

2020 ◽

Vol 11 (1) ◽

pp. 17

Author(s):

Kalevi Kairemo ◽

S. Cheenu Kappadath ◽

Timo Joensuu ◽

Homer A. Macapinlac

Keyword(s):

Prostate Cancer ◽

Cell Membrane ◽

Sodium Fluoride ◽

Bone Mineralization ◽

Membrane Lipid ◽

Skeletal Metastases ◽

Study Cohort ◽

Skeletal Disease ◽

Sclerotic Bone ◽

Pet Ct

Bone metastases are common in prostate cancer (PCa). Fluorocholine-18 (FCH) and sodium fluoride-18 (NaF) have been used to assess PCa associated skeletal disease in thousands of patients by demonstrating different mechanism of uptake-cell membrane (lipid) synthesis and bone mineralization. Here, this difference is characterized quantitatively in detail. Our study cohort consisted of 12 patients with advanced disease (> 5 lesions) (M) and of five PCa patients with no skeletal disease (N). They had routine PET/CT with FCH and NaF on consecutive days. Skeletal regions in CT were used to co-register the two PET/CT scans. Bone 3-D volume of interest (VOI) was defined on the CT of PET with a threshold of HU > 150, and sclerotic/dense bone as HU > 600, respectively. Additional VOIs were defined on PET uptake with the threshold values on both FCH (SUV > 3.5) and NaF (SUV > 10). The pathologic skeletal volumes for each technique (CT, HU > 600), NaF (SUV > 10) and FCH (SUV > 3.5) were developed and analyzed. The skeletal VOIs varied from 5.03 L to 7.31 L, whereas sclerotic bone VOIs were from 0.88 L to 2.99 L. Total choline kinase (cell membrane synthesis) activity for FCH (TCA) varied from 0.008 to 4.85 [kg] in M group and from 0.0006 to 0.085 [kg] in N group. Total accelerated osteoblastic (bone demineralization) activity for NaF (TBA varied from 0.25 to 13.6 [kg] in M group and varied from 0.000 to 1.09 [kg] in N group. The sclerotic bone volume represented only 1.86 ± 1.71% of the pathologic FCH volume and 4.07 ± 3.21% of the pathologic NaF volume in M group, and only 0.08 ± 0.09% and 0.18 ± 0.19% in N group, respectively. Our results suggest that CT alone cannot be used for the assessment of the extent of active metastatic skeletal disease in PCa. NaF and FCH give complementary information about the activity of the skeletal disease, improving diagnosis and disease staging.

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