Types Of Bone Metastases Research Articles

A new era in the management of spinal metastasis.

Despite the recent advances in cancer treatment, the incidence of patients with spinal metastases continues to grow along with the total number of cancer patients. Spinal metastases can significantly impair activities of daily living (ADL) and quality of life (QOL), compared with other types of bone metastases, as they are characterized with severe pain and paralysis caused by skeletal-related events. Reduced ADL can also lead to treatment limitations as certain anticancer agents and radiation therapy are not compatible treatments; thus, leading to a shorter life expectancy. Consequently, maintaining ADLs in patients with spinal metastases is paramount, and spine surgeons have an integral role to play in this regard. However, neurosurgeon, orthopedic and spinal surgeons in Japan do not have a proactive treatment approach to spinal metastases, which may prevent them from providing appropriate treatment when needed (clinical inertia). To overcome such endemic inertia, it is essential for 1) spine surgeons to understand and be more actively involved with patients with musculoskeletal disorders (cancer locomo) and cancer patients; 2) the adoption of a multidisciplinary approach (coordination and meetings not only with the attending oncologist but also with spine surgeons, radiologists, rehabilitation specialists, and other professionals) to preemptive treatment such as medication, radiotherapy, and surgical treatment; and 3) the integration of the latest findings associated with minimally invasive spinal treatments that have expanded the indications for treatment of spinal metastases and improved treatment outcomes. This heralds a new era in the management of spinal metastases.

Abstract A007: Preclinical bone metastasis technology platform – Predictive evaluation of experimental therapies on bone metastasis

Abstract Most cancer deaths are due to metastases, and bone metastases are a considerable problem especially in breast and prostate cancer, being developed in 70-90% of advanced-stage patients. Despite major investments in oncology drug development, bone metastases are currently incurable and a high unmet medical need with only 5% of patients being alive 5 years after the diagnosis. Development of therapies for bone metastasis has been challenging due to lack of appropriate preclinical models available to support decision making in next phases of drug development. In the absence of clinically relevant preclinical bone metastasis models, the current strategy is to rely on preclinical efficacy data obtained with subcutaneous models that lack the clinically relevant local tissue microenvironment, which has a major impact on tumor growth. The use of clinically non-relevant models in preclinical-stage development may be one important reason for the current >95% failure rate of oncology drugs in clinical trials. To support predictive evaluation of therapies for bone metastatic cancers, we describe a preclinical bone metastasis technology platform for evaluating efficacy of novel therapies on bone metastases. The platform utilizes tumors growing in bone microenvironment, mimicking growth of bone metastases in patients. Syngeneic or humanized mouse models with tumor and immune cells of same species are needed for supporting development of immunotherapies, allowing interactions of tumor and immune cells in the bone metastatic microenvironment, according to the novel osteoimmuno-oncology concept. The platform provides a predictive tool for studying unique biological features associated with different types of bone metastases in cancer-type specific manner. Here we summarize case examples where results from preclinical bone metastasis studies align with clinical findings of different therapies approved or evaluated for bone metastasis. Zoledronic acid, an anti-resorptive bisphosphonate that is currently used in breast cancer patients with bone metastases to prevent cancer-induced bone loss, showed improved bone health but no effects on tumor growth. Radium-223 dichloride, an approved treatment for bone metastatic castration-resistant prostate cancer in patients, showed reduced prostate cancer growth and decreased tumor-induced bone changes. As for immunotherapies, an IDO1 inhibitor had no effects on breast cancer bone metastases and the anti-PD-1 antibody pembrolizumab had no effects on breast and prostate cancer bone metastases, predicting recent clinical findings that demonstrate lack of efficacy of anti-PD-1 in clinical prostate cancer trials. We conclude that the bone metastasis technology platform is a biologically relevant tool for preclinical evaluation of the efficacy of experimental therapies on bone metastasis, and it has been validated with positive and negative case examples, demonstrating its clinically predictive power. Citation Format: Tiina E Kähkönen, Jussi M Halleen, Jenni Bernoulli. Preclinical bone metastasis technology platform – Predictive evaluation of experimental therapies on bone metastasis [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr A007.

Osteolytic or mixed bone metastasis is not uncommon in patients with high-risk prostate cancer

PurposeOsteolytic or mixed bone metastases (BMs) are considered rare in prostate cancer (PCa). However, we hypothesized that they are not uncommon in high-risk PCa. This study aimed to compare the clinical and CT imaging characteristics of PCa by focusing on BMs among patients with Gleason score (GS) ≥ 8 (high-risk group) and those with GS ≤ 7 (intermediate-low-risk group). MethodsBetween 2014 and 2021, patients with pathologically proven PCa and no history of other malignancies were included. Clinical findings including age and prostate-specific antigen (PSA) were collected. CT imaging findings, including the types of BM and other metastases, were evaluated by two radiologists. The clinical and CT imaging findings were compared between the high- and intermediate-low-risk groups. ResultsPatients were classified into high-risk (n = 527) and intermediate-low-risk (n = 973) groups. Age at diagnosis (median: 71 [44–91] vs 69 [35–86] years, p < 0.0001), PSA (8.7 [0.01–15314.5] vs 5.8 [0.01–163.2] ng/mL, p < 0.0001), frequencies of BMs (osteoblastic: 47/527 [8.7%] vs 3/973 [0.3%]), osteolytic or mixed BM (19/527 [3.6%] vs 2/973 [0.2%]), lymph node metastases (76/527 [14.4%] vs 3/973 [0.3%]), and lung metastases (13/527 [2.5%] vs 0%) were significantly higher in the high-risk group than in the intermediate-low-risk group (all p < 0.0001). ConclusionsAge, PSA, and the frequencies of osteolytic or mixed BMs were significantly higher in the high-risk group than in the intermediate-low-risk group. This study highlights the importance of high-risk PCa in the differential diagnoses of osteolytic or mixed BMs.

Bone Metastases of Diverse Primary Origin Frequently Express the VDR (Vitamin D Receptor) and CYP24A1.

Active vitamin D (1,25(OH)2D3) is known to exert direct anti-cancer actions on various malignant tissues through binding to the vitamin D receptor (VDR). These effects have been demonstrated in breast, prostate, renal and thyroid cancers, which all have a high propensity to metastasise to bone. In addition, there is evidence that vitamin D catabolism via 24-hydroxylase (CYP24A1) is altered in tumour cells, thus, reducing local active vitamin D levels in cancer cells. The aim of this study was to assess VDR and CYP24A1 expression in various types of bone metastases by using immunohistochemistry. Overall, a high total VDR protein expression was detected in 59% of cases (39/66). There was a non-significant trend of high-grade tumours towards the low nuclear VDR expression (p = 0.07). Notably, patients with further distant metastases had a reduced nuclear VDR expression (p = 0.03). Furthermore, a high CYP24A1 expression was detected in 59% (39/66) of bone metastases. There was a significant positive correlation between nuclear VDR and CYP24A1 expression (p = 0.001). Collectively, the VDR and CYP24A1 were widely expressed in a multitude of bone metastases, pointing to a potential role of vitamin D signalling in cancer progression. This is of high clinical relevance, as vitamin D deficiency is frequent in patients with bone metastases.

PSAT164 Incidence and Severity of Hypocalcemia in Association with Antiresorptive Therapy in Cancer Patients with Bone Metastasis: An Integrated Health Network Experience

Abstract Introduction Antiresorptive therapy (ArT) has been known to decrease the risk of skeletal-related events (SRE), such as bone pain and pathological fractures, in cancer patients with bone metastasis (BM). While beneficial, ArT may cause adverse effects in this population including hypocalcemia, which can be severe and life-threatening. We examined the incidence, severity, and risk factors for hypocalcemia associated with the use of ArT to treat BM in cancer patients. Methods We conducted a retrospective review of the electronic medical records of adult patients with advanced cancer complicated by BM who were treated at our institution between January 2016 and November 2020. Our primary aim was to compare the incidence and severity of hypocalcemia with the use of IV Zoledronic acid (ZA), a bisphosphonate, vs SQ Denosumab (DM), a RANKL inhibitor, to treat BM in cancer patients.Our secondary aim was to compare risk factors associated with severe hypocalcemia (defined as albumin-corrected serum calcium &amp;lt; 7 mg/dL). Inclusion criteria were patients aged 19-99 years with a history of cancer with known BM, who received either ZA or DM. Results We reviewed 860 EMRs of patients treated within the specified period. 392 patients met inclusion criteria, among them, 297 (76%) and 95 (24%) received DM and ZA, respectively. There were no between-group differences in age, ethnicity, or weight. The median patient age was 71 years (range: 27–96). There were, however, between-group differences in gender (p=0.01) and cancer diagnoses (p=0.03). Females comprised 53.9% of the DM group vs. 40% of the ZA group. The top three cancer diagnoses were (DM vs ZA groups): breast (40.1% vs 26.3%), prostate (25.9% vs 40%), and lung cancer (17.8% vs 15.8%). Overall incidence of hypocalcemia was 48.8% (n=144) and 45.3% (n= 43) with the use of DM and ZA, respectively (p=NS). Severe hypocalcemia was more frequently observed with the use of DM vs ZA (6.6% vs 1.1%, p &amp;lt;0.05). Median (IQR) corrected serum calcium concentration following ArT (when trending calcium for the individual patient) was 8.4 (7.9-8.8) and 8.6 (8.2-8.8) mg/dL for DM a ZA groups, respectively (p=0.1). There were no between-group differences in risk factors for hypocalcemia, such as renal function (eGFR), concentrations of 25-hydroxy vitamin D, albumin, phosphorus, magnesium, or TSH. However, there was a between-group difference in the concentration of alkaline phosphatase (median 83 vs 101 IU/L for DM vs ZA, p= 0.02). There were no between-group differences in the type of BM (osteolytic vs osteoblastic, p=0.9) Conclusion: Severe hypocalcemia was significantly more common with the use of DM compared to ZA for the treatment of BM in cancer patients treated at our institution. Our study was limited by its retrospective design and the between-group differences in gender distribution and cancer diagnoses. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Imaging features inferring symptom onset due to spinal metastasis progression: a preliminary study.

Spinal metastases can cause intractable pain and neurological deficits, which can markedly worsen both patients' activities of daily living (ADL) and their health-related quality of life (QOL). Early intervention is essential to prevent irreversible neurological deficits and pain associated with spinal metastases. We investigated the imaging features of spinal metastases that led to neurological deficits. We analyzed axial cross-sectional computed tomography (CT) images of cervical and thoracic spinal metastases in patients with and without lower limb motor paralysis, neuropathic pain, and local nociceptive pain. We distinguished regions of the spine associated with these respective symptoms, and explored their inferable performance using images obtained before symptom onset. In addition, we analyzed the imaging features and type of bone metastasis (osteolytic and osteoblastic). Spinal lesions occupied the area in and around the spinal canal and around the pedicle in patients with motor paralysis. Lesions around the pedicle and in the most posterior vertebral body part before symptom onset were inferable. In patients with neuropathic pain, spinal metastases spread along the pedicle before symptom onset, and had surrounded the spinal canal circumferentially at symptom onset. Local nociceptive pain was more common near the center of the vertebral body either at or before symptom onset. There was no difference in the imaging features according to the type of bone metastasis. Lesions in certain regions in the asymptomatic metastatic spine can indicate the onset of spinal metastasis-related symptoms in the next few months. Early therapeutic intervention might be applied to prevent neurological disorder.

Characterization of bone metastases detected on 68Ga-PSMA PET/CT in newly diagnosed prostate cancer.

This study sought to investigate the characteristics of bone metastasis (BM) and the association of BM with clinicopathological factors in prostate cancer (PCa) patients presenting with BM on the initial staging gallium-68-prostate-specific membrane antigen (68Ga-PSMA) positron emission tomography/computed tomography (PET/CT). Patients with at least one BM in the initial staging 68Ga-PSMA PET/CT between January 2018 and December 2021 were reviewed retrospectively. Types of BM were classified according to 68Ga-PSMA PET/CT findings as osteoblastic (OB), osteolytic (OL), intramedullary (IM) and coexistence of these types. Patients were divided into two groups according to the number of BM: Oligo-BM for those with five or fewer BMs and poly-BM for those with more than five BM. Receiver-operating characteristic (ROC) curves were generated for serum bone-specific alkaline phosphatase (ALP) and prostate-specific antigen (PSA) levels to discriminate between oligo-BM and poly-BM groups. Univariate and multivariate logistic regression tests were performed to find independent predictors of poly-BM. A total of 53 patients with a median age of 70 (range: 49-88) were included in the study. The median Gleason score of the patients was 8 (range: 6-10). Among the patients, 23 had solely OB-type; 10 had solely IM type; 12 had OB and IM type; four had IM and OL type, two had OB and OL type; one had solely OL type, and one had IM and OB and OL type BM. Oligo-BM was detected in 25 patients (47.2%) and poly-BM was detected in 28 patients (52.8%). In multivariate analyses, serum ALP levels ≥122U/L and PSA levels ≥85.4ng/mL were found to be independent predictors of poly-BM. In characterizing BM of PCa, we found that OB-type metastases were the most common type, followed by IM-type and OL-type metastases, respectively. High ALP and PSA levels were found to be independent predictors of poly-BM.

Efficacy of 3 Monthly versus Monthly Zoledronic Acid on Bone Metastasis

Background: Bone metastatic disease affect a patient’s quality of life. Aim: Evaluating possible stratification factors affecting the efficacy of different schedules of zoledronic acid on SREs. Patients and Methods: A randomized, clinical trial at Zagazig university hospitals. 108 Patients were enrolled to receive zoledronic acid 4 mg (A and B groups=12 and 4 weeks, respectively) for 2 years. Results: Regarding age, tumour type, types of bone metastasis and number of bone metastasis, there was an insignificant difference between both groups. However, 3 monthly regimen of zoledronic acid gave better results in solitary than multiple bone metastases. Regarding pretreatment ECOG, there was an insignificant difference between between both groups. However, 3 monthly regimen of zoledronic acid gave better results in pre-treatment ECOG 1and ECOG 2 than ECOG 3. Conclusion: A 3-monthly regimen of zoledronic acid is more effective in management of solitary or few sites of bone metastasis, osteoblastic bony lesions and patients with good performance status. Recommendations: We recommend a larger sample size and the study should include a homogenous groups of patients so we can judge well on different stratifications factors that can affect efficacy of 3- monthly regimen of zoledronic acid.

Determination Of Risk Parameters In The Detection Of Asymptomatic Bone Metastases Of Kidney And Prostate Cancer

Using multivariate analysis to identify predictive risk parameters in the diagnosis of asymptomatic osteogenic metastasis of renal and prostate cancer. The work was based on the results of observations of 105 patients with a morphologically confirmed diagnosis of malignant neoplasm registered at the Republican Specialized Scientific and Practical Center of Oncology and Radiology (RSNPMTSO and R) and the Samarkand branch. In 62 patients with kidney cancer (RP) included in the study, the mean age of patients with RP was 58.3 years. 43 patients with prostate cancer (PC) were included in the study, the average age of patients with PC was 68 years. We analyzed such parameters as age, stage of the disease, timing of detection of bone metastasis (BM), prevalence, type and size of BM, as well as additional criteria: in case of prostate cancer - the size of the primary tumor and the degree of malignancy, in case of prostate cancer - the sum of points on the Gleason scale and the prostate -specific antigen (PSA). It was revealed that the highest risk in detecting BM in RP was noted for the stage of the disease, p = 0.006. Also, a high risk was associated with the size and grade of tumor malignancy, with CR at p = 0.006 and p = 0.008, respectively. Among the listed, the highest risk in detecting BM is observed in prostate cancer for the stage of the disease (p = 0.001). In addition, an increased risk was observed for the Gleason score and PSA level (p = 0.013 and p = 0.008, respectively). Thus, during the 2-year follow-up, BM most often develops in patients with kidney cancer at stage Tv-T3a stage and with grade G III and in patients with prostate cancer - in the presence of stage III with a Gleason score of ≥ 7 and a level PSA in the range of 21-50 ng / ml.

Abstract PS14-22: Clinical characteristics, prognostic factors and treatment comes of patients with bone-only metastatic breast cancer

Abstract Introduction: Despite efforts in advancing early detection programs, 5-20% of breast cancer patients present with distant metastases at diagnosis. Bone is the most frequent site of breast cancer metastasis, noted in 60-80% of metastatic breast cancer (MBC) patients, and is the first site of metastatic disease in 25-40% of patients. The outcome of patients with bone-only MBC (BOM) is usually better than those with visceral metastasis. However, differences between those who present with De-novo BOM and those who progress to bone-only disease following a diagnosis of early stage breast cancer is not clear. Such differences in clinical course might have an implication on aggressiveness of treatment.The aim of the study is to present the clinical and pathological features along with treatment outcomes of breast cancer patients with BOM in relation to timing and type of bone metastasis. Known prognostics factors that affects treatment outcome will be presented.Patients and Methods: Patients with De-novo and those who progressed after an initial diagnosis of early-stage breast cancer with bone-only metastasis diagnosed, treated and followed up at our institution between 2006 and 2018 were included. Data related to characteristic such as, grade, hormonal status, HER-2 status were collected from our electrical medical records, pathology and radiology reports. De-novo BOM was defined as bone metastasis diagnosed at presentation or within the first 4 months of follow up. Results: A total of 242 patients fulfilled our inclusion criteria and were included in the analysis. The median age (range) at diagnosis was 52 (27-80) years. Majority of the patients (77.3%) had De-novo BOM and multiple sites of bone involvement was identified in 82.6%. High- grade (G-III), HER2-positive and hormone receptor (HR)-negative disease were identified in 27.2%, 18.2% and 8.7%, respectively. Majority of the patients were treated with endocrine therapy while 31(12.9%) patients received chemotherapy at presentation.With a median follow up of 37.7 months, 185 (76.4%) of patients progressed, the median time to progression was 17.1 months (range 3-280m). The median overall survival (OS) for patients with de novo BOM disease was significantly shorter than those who developed subsequent bone metastasis; 40.8 months (95% CI, 51.1-184.1) compared to 80.9 months (95% CI, 36.4-47.9), p &amp;lt; 0.001. Tumor grade, HR status and type of bone lesions (lytic or sclerotic) have significant impact on 5-year OS as detailed in Table-1 Conclusions: Bone-only metastasis breast cancer is distinct clinical entity with a favorable prognosis and a prolonged overall survival. Several risk features for poor OS were identified and might be useful tool to design future clinical trials to trigger upscaling endocrine therapy to include newly introduced resistance modulating agents. Characteristics5-year Progression-Free Survival5-year Overall SurvivalPercentageP-valuePercentageP-valueAge (year)&amp;lt;5022.70.5544.90.21≥5022.739.2Tumor gradeI27.30.00564.90.01II23.343.6III9.626.6HER2Negative23.10.0343.60.79Positive15.632.9Estrogen receptors (ER)Negative16.30.1513.70.005Positive23.144.5Progesterone receptors (PR)Negative17.70.0920.60.004Positive23.345.5Number of bone lesionsMultiple20.60.0839.10.08Single34.554.8Type of bone metastasisLytic28.20.9346.00.01Sclerotic21.554.9Mixed14.643.0Time of bone metastasisDe novo13.4&amp;lt;0.00135.5&amp;lt;0.001Late49.060.5 Citation Format: Lina Marei, Dina Braik, Ayat Taqash, Hikamt Abdel-Razeq. Clinical characteristics, prognostic factors and treatment comes of patients with bone-only metastatic breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS14-22.

Clinical characteristics and prognosis of renal cell carcinoma patients with bone metastases

Objective: To determine the status of bone metastasis (BM) and prognosis factors of patients with renal cell carcinoma (RCC) in our center. Methods: The clinical and medical records of RCC patients with BM, who were admitted to the Department of Urology, Bone Oncology and Spine Surgery, Beijing Jishuitan Hospital from August 2009 to August 2017 were collected. The gender, age, time of BM, location of BM, numbers of BM, presence or absence of visceral metastasis, pathological types of BM were investigated. The patients were followed up regularly, and the survival curves were analyzed by Kaplan-Meier method. Cox proportional hazard regression model was used to estimate the prognostic factors. Results: A total of 51 RCC patients with bone metastasis were collected. The age of patients ranged from 38 to 76 (58.6±8.2) years old, including 39 males (76.5%) and 12 females (23.5%). The ratio of male to female was 3.25∶1. The patients were followed up for 8 to 109 months, with a median follow-up time of 30 months. The follow-up rate was 90.2%. Thirty-one (60.8%) patients died at the last follow-up, with a median overall survival (OS) time of 25 months. The median OS was 38 months and 20 months in the solitary BM group (26 cases, 51.0%) and BM ≥ 2 group (25 cases, 49.0%), respectively. The difference between the two groups was statistically significant (P=0.021). The median OS was 30 months, 69 months and 17 months in the axis BM group (22 cases, 43.1%), appendicular BM group (19 cases, 37.3%) and both the axis and appendicular BM group (10 cases, 19.6%), respectively. The difference between the groups was statistically significant (P=0.012). The median OS was 22 months and 38 months in the patients with (15 cases, 29.4%) and without (36 cases, 70.6%) visceral metastases groups, respectively. The difference between the two groups was statistically significant (P=0.007). Univariate and multivariate Cox regression analysis showed that the numbers of BM (HR=3.130, 95%CI: 1.502-6.520, P=0.035) and visceral metastasis (HR=4.699, 95%CI: 1.810-9.545, P=0.001) were independent prognostic factors for RCC with BM. Conclusions: Solitary BM, no visceral metastasis are good prognostic factors for RCC with BM. For these patients, radical resection of BM is feasible to improve survival rate.

Analysis of metastatic involvement in bone using anatomical and functional information from 18F-FDG PET/CT.

Although the overall incidence of bone metastasis is not known, over one-half of the people who die of cancer in the USA every year are thought to have bone involvement. In this study we have developed a method to quantify the metabolic and anatomic changes induced by different types of bone metastases in cancer patients using PET/CT images. Seventy-three cancer patients with no previous history of chemotherapy or radiotherapy who had definite bone metastases documented by PET/CT and other conventional modalities were selected for this study. PET and computed tomography (CT) images were resampled to the same pixel size. Thereafter, the bone structure was segmented using thresholding. The 50% of the maximum standardized uptake value within the bone mask was used to identify bone lesions in each slice. Using the final regions of interest defined at 70% of the maximum, the lesion characteristics including the mean Hounsfield Units were computed from the PET/CT images. The lesions were subjected to visual confirmation by an experienced physician who also categorized them on the basis of the appearances in CT as lytic, sclerotic, mixed, or no-change type. The lesion characteristics were compared using statistical methods. In all, 340 bony lesions in 73 patients with different cancer types were analyzed. The lesions were further categorized into four groups on the basis of their anatomical location. The spine hosts the largest number of lesions. The lumbar bones are the most preferential sites within the spine. Statistical comparison of CT values indicated that the difference between no-change and lytic types was significant. Uptake period did not seem to have a significant impact on no-change and sclerotic types. Quantitatively, maximum standardized uptake value for lytic, no change, mixed, and sclerotic lesions were 7.4, 6.1, 8.2, and 7.2, respectively. A quantitative method provides a convenient way that may serve as a useful tool in monitoring and assessing the response to therapy.

68Ga]PSMA-HBED-CC Uptake in Osteolytic, Osteoblastic, and Bone Marrow Metastases of Prostate Cancer Patients.

The aim of this study was to evaluate potential differences in "Glu-NH-CO-NH-Lys" radio-labeled with [68Ga]gallium N,N-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N-diacetic acid ([68Ga]PSMA-HBED-CC) uptake in osteolytic, osteoblastic, mixed, and bone marrow metastases in prostate cancer (PC) patients. This retrospective study was approved by the local ethics committee. Patients who received [68Ga]PSMA-HBED-CC positron emission tomography/computed tomography ([68Ga]PSMA-PET/CT) with at least one positive bone metastasis were included in this study. Only patients who have not received systemic therapy for their PC were included. Bone metastases had to be confirmed by at least one other imaging modality or follow-up investigation. The maximum standardized uptake value (SUVmax) and mean Hounsfield units (HUmean) of each metastasis were measured. Based on CT, each metastasis was classified as osteolytic (OL), osteoblastic (OB), bone marrow (BM), or mixed (M). One hundred fifty-four bone metastases in 30 patients were evaluated. Eighty out of 154 (51.9%) metastases were classified as OB, 21/154 (13.6%) as OL, 23/154 (14.9%) as M, and 30/154 (19.5%) as BM. The SUVmax for the different types of metastases were 10.6±7.07 (OB), 24.0±19.3 (OL), 16.0±21.0 (M), and 14.7±9.9 (BM). The SUVmax of OB vs. OL and OB vs. BM metastases differed significantly (p≤0.025). A significant negative correlation between HUmean and SUVmax (r=-0.23, p<0.05) was measured. [68Ga]PSMA-HBED-CC uptake is higher in osteolytic and bone marrow metastases compared to osteoblastic metastases. Information derived from [68Ga]PSMA-PET and CT complement each other for the reliable diagnosis of the different types of bone metastases in PC patients.

Temporal Subtraction of Serial CT Images with Large Deformation Diffeomorphic Metric Mapping in the Identification of Bone Metastases

Purpose To determine the improvement of radiologist efficiency and performance in the detection of bone metastases at serial follow-up computed tomography (CT) by using a temporal subtraction (TS) technique based on an advanced nonrigid image registration algorithm. Materials and Methods This retrospective study was approved by the institutional review board, and informed consent was waived. CT image pairs (previous and current scans of the torso) in 60 patients with cancer (primary lesion location: prostate, n = 14; breast, n = 16; lung, n = 20; liver, n = 10) were included. These consisted of 30 positive cases with a total of 65 bone metastases depicted only on current images and confirmed by two radiologists who had access to additional imaging examinations and clinical courses and 30 matched negative control cases (no bone metastases). Previous CT images were semiautomatically registered to current CT images by the algorithm, and TS images were created. Seven radiologists independently interpreted CT image pairs to identify newly developed bone metastases without and with TS images with an interval of at least 30 days. Jackknife free-response receiver operating characteristics (JAFROC) analysis was conducted to assess observer performance. Reading time was recorded, and usefulness was evaluated with subjective scores of 1-5, with 5 being extremely useful and 1 being useless. Significance of these values was tested with the Wilcoxon signed-rank test. Results The subtraction images depicted various types of bone metastases (osteolytic, n = 28; osteoblastic, n = 26; mixed osteolytic and blastic, n = 11) as temporal changes. The average reading time was significantly reduced (384.3 vs 286.8 seconds; Wilcoxon signed rank test, P = .028). The average figure-of-merit value increased from 0.758 to 0.835; however, this difference was not significant (JAFROC analysis, P = .092). The subjective usefulness survey response showed a median score of 5 for use of the technique (range, 3-5). Conclusion TS images obtained from serial CT scans using nonrigid registration successfully depicted newly developed bone metastases and showed promise for their efficient detection. © RSNA, 2017 Online supplemental material is available for this article.

Characterization of bone only metastasis (BOM) patients (pts) with respect to tumor subtypes (TS).

1072 Background: Metastatic breast cancer (MBC) pts with BOM are a unique population with limited characterization. Our goal was to characterize the TS of BOM pts, evaluating differences in sites and types of bone metastases (BM), treatment, and survival. Methods: We identified pts followed at MD Anderson Cancer Center from 01/01/1997 to 12/31/2015 for at least 6 months with a BOM diagnosis as first site of metastasis (met). TS was assessed by initial biopsy immunohistochemistry (IHC) (Table 1) with hormone receptor (HR) + defined as ER or PR &gt;10%. Results: We identified 1445 pts with BOM, 1049 with initial biopsy IHC available to group into TS (Table 1). Among BOM pts, the majority had multiple BM at diagnosis (1141/79%), most in both the axial (Ax) and appendicular (App) skeleton (53%). Of the 808 pts with BM categorized on imaging at diagnosis, the majority were lytic (389/48%), with 21% sclerotic, 18% mixed, and 12% blastic. Time from breast cancer diagnosis to first met differed significantly by TS, χ2(3) = 94.33, P&lt; .0001, with median time to met longer for pts with blastic (3.08 years; 95% CI 2.03, 4.24) versus lytic lesions (1.75 years; 95% CI 1.27, 2.17). Conclusions: BOM patients are a unique MBC subpopulation, more commonly found in luminal TS patients. Our study demonstrates prognostic differences in BOM pts specific to TS and emphasizes the need for further study of BOM patients. [Table: see text]

Influence of the Different Primary Cancers and Different Types of Bone Metastasis on the Lesion-based Artificial Neural Network Value Calculated by a Computer-aided Diagnostic System, BONENAVI, on Bone Scintigraphy Images.

Objective(s):BONENAVI, a computer-aided diagnostic system, is used in bone scintigraphy. This system provides the artificial neural network (ANN) and bone scan index (BSI) values. ANN is associated with the possibility of bone metastasis, while BSI is related to the amount of bone metastasis. The degree of uptake on bone scintigraphy can be affected by the type of bone metastasis. Therefore, the ANN value provided by BONENAVI may be influenced by the characteristics of bone metastasis. In this study, we aimed to assess the relationship between ANN value and characteristics of bone metastasis.Methods:We analyzed 50 patients (36 males,14 females; age range: 87–42 yrs median age:72.5 yrs) with prostate, breast, or lung cancer who had undergone bone scintigraphy and were diagnosed with bone metastasis (32 cases of prostate cancer, nine cases of breast cancer, and nine cases of lung cancer). Those who had received systematic therapy over the past years were excluded. Bone metastases were diagnosed clinically, and the type of bone metastasis (osteoblastic, mildly osteoblastic, osteolytic, and mixed components) was decided visually by the agreement of two radiologists. We compared the ANN values (case-based and lesion-based) among the three primary cancers and four types of bone metastasis.Results:There was no significant difference in case-based ANN values among prostate, breast, and lung cancers. However, the lesion-based ANN values were the highest in cases with prostate cancer and the lowest in cases of lung cancer (median values: prostate cancer, 0.980; breast cancer 0.909; and lung cancer, 0.864). Mildly osteoblastic lesions showed significantly lower ANN values than the other three types of bone metastasis (median values: osteoblastic,; 0.939 mildly osteoblastic; 0.788, mixed type; 0.991, and osteolytic. 0.969) The possibility of a lesion-based ANN value below 0.5 was %10.9 for bone metastasis in prostate cancer, %12.9 for breast cancer, and %37.2 for lung cancer. The corresponding possibility were %14.7 for osteoblastic metastases, %23.9 for mildly osteoblastic metastases, %7.14 for mixed-type metastases, and %16.0 for osteolytic metastases.Conclusion:The lesion-based ANN values calculated by BONENAVI can be influenced by the type of primary cancer and bone metastasis.

PSA affects prostate cancer cell invasion in vitro and induces an osteoblastic phenotype in bone in vivo

Patients with advanced prostate cancer frequently have a poor prognosis as a result of metastasis and present with high serum PSA levels. There is evidence suggesting that the serine protease activity of PSA could be involved in the invasion and metastasis of prostate cancer. In this study, we determined the effects of PSA and its precursor, pro-PSA, on invasion and the type of bone metastasis. We stably transfected prostate adenocarcinoma cells, human DU-145 and rat MatLyLu, with either the full-length prepro-PSA sequence or pre-PSA DNA, to generate subclones of cells that secrete pro-PSA or free PSA, respectively. Secretion of PSA was measured by western blot analysis and enzyme-linked immunosorbent assay (ELISA). The invasive and migratory properties of the cells were determined using a basement membrane extract and were compared with corresponding empty vector control cells. Twelve days after injection of PSA-secreting MatLyLu cells into the femora of nude mice, bone tumor burden and histomorphometry were determined using a stereological technique. The transfected cells secreted 0.15-2.23 ng PSA/10(6) cells/day. Pro-PSA-secreting subclones increased invasion and migration by 24-263%. Conversely, the PSA-secreting subclones significantly reduced both invasion and migration by 59-70%. The divergent effects on invasion and migration observed in pro-PSA- and PSA-secreting subclones indicate that different forms of PSA may have different functions. Intrafemoral injections with PSA-secreting MatLyLu cells resulted in an increase in osteoblastic parameters when compared with non-PSA-secreting subclones as measured by bone histomorphometry. Concomitantly, a decrease in osteoclasts and eroded surface was observed. Our in vitro data suggest that PSA, dependent on the predominant form secreted, may decrease or increase invasive properties of prostate cancer cells. The in vivo results indicate that PSA in the bone microenvironment may contribute to the osteoblastic phenotype of bone metastasis frequently observed in prostate cancer.

Types of bone metastases in women with breast cancer undergoing systemic treatments

Types of bone metastases in women with breast cancer undergoing systemic treatments

Histopathological observations on osteolytic bone metastasis

Three types of bone metastasis can be identified : the osteolytic, osteoblastic and the intertrabecular metastasis. Bone resorption is believed to be responsible for osteolytic metastasis. The early stage of metastatic lesion showed tumor cells loosely intermingled with osteoblasts, fibroblastic stromal cells, osteoclasts and endothelial cells. In the metastatic nest, many tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts accumulated in direct contact with alkaline phosphatase (ALP)--or receptor activator of NF-kappaB ligand (RANKL)-positive osteoblastic cells, indicating the osteoclastogenesis. On the other hand, osteoclasts express CD44 while osteopontin was abundant in the stromal tissue of tumor nests. Therefore, mediating its affinity for CD44, osteopontin may serve to facilitate osteoclastic migration. We review the histopathological microenvironment featuring osteoclastic bone resorption, angiogenesis and matrix degradation, which appears to facilitate proliferation of tumor cells after the onset of bone metastasis.

Differential expression of osteopontin and bone sialoprotein in bone metastasis of breast and prostate carcinoma.

Breast and prostate cancer often metastasise to the skeleton. Interestingly, the histopathological characteristics of the bone lesions that arise from these two cancer types differ. Breast tumours give rise to metastases in the skeleton with a mixed lytic/sclerotic pattern, whereas a predominantly sclerotic pattern is seen in metastases from prostate tumours. Osteopontin (OPN) and bone sialoprotein (BSP) are bone matrix proteins that have been implicated in the selective affinity of cancer cells for bone. In the present study, 21 patient cases with skeletal metastasis and their respective primary tumours (12 with breast cancer, 9 with prostate cancer) were investigated by immunohistochemistry in order to assess the level of OPN and BSP. Moderate to strong OPN expression was found in 42% of all breast tumours and in 56% of all prostate tumours. Significantly more breast cancer bone metastases exhibited high OPN expression, 83%, as compared with prostate tumour bone metastases, 11% (P = 0.0019). In contrast, moderate to strong BSP expression was found in 33% of breast tumours and in 89% of prostate tumours. In the bone lesions, only 33% of breast tumour metastases showed moderate/strong BSP expression compared to 100% of prostate tumour metastases (P = 0.0046). This divergent pattern of OPN/BSP expression could be an important determinant for the different characteristics of these two types of bone metastasis, i.e., lytic vs. sclerotic, consistent with the proposed role of OPN in differentiation and activation of osteoclasts and of BSP as a stimulator of bone mineralisation.