Occurrence Of Bone Metastases Research Articles

Development and validation of a diagnostic and prognostic model for bone metastasis of intrahepatic cholangiocarcinoma: a population-based analysis.

Bone metastasis (BM) is a common site of metastasis in patients with intrahepatic cholangiocarcinoma (ICC), significantly impacting the quality of life and prognosis of affected individuals. This investigation aimed to assess the risk of BM development in ICC patients and to prognosticate for patients with ICC-associated BM (ICCBM) through the construction of two nomograms. We conducted a retrospective analysis of data from 2,651 ICC patients, including 148 cases of BM, documented in the Surveillance, Epidemiology, and End Results (SEER) database spanning 2010 to 2017. Independent predictors for the occurrence of BM in ICC patients were identified via univariate and multivariate logistic regression analyses; simultaneously, independent prognostic indicators for ICCBM patients were ascertained through univariate and multivariate Cox regression analyses. The utility of the nomograms was evaluated through calibration curves, receiver operating characteristic (ROC) curves, decision curve analysis (DCA), and Kaplan-Meier (KM) analysis. Independent risk factors for BM in ICC included sex, tumor size, lung metastasis, brain metastasis, and intrahepatic metastasis. For ICCBM patients, independent prognostic factors comprised age, chemotherapy, and radiotherapy. The prognostic nomogram exhibited C-indexes of 0.737 [95% confidential interval (CI): 0.682-0.792] for the training cohort and 0.696 (95% CI: 0.623-0.769) for the validation cohort. Calibration curves demonstrated strong concordance between predicted outcomes and observed events. The areas under the curve (AUC) for 3-, 6-, and 12-month cancer-specific survival (CSS) were 0.853, 0.781, and 0.739, respectively, in the training cohort, and 0.794, 0.822, and 0.780 in the validation cohort. DCA illustrated significant net benefits across a broad spectrum of threshold probabilities. KM analysis revealed 1-, 2-, and 3-year CSS rates of 23.91%, 7.55%, and 2.35%, respectively, with a median CSS of 6 months, underscoring the nomograms' capacity to distinctly stratify patients according to survival risk. The development of these nomograms offers substantial clinical utility in forecasting BM risk among ICC patients and prognosticating for those with ICCBM, thereby facilitating the formulation of more efficacious treatment modalities.

Development and validation of an early diagnosis model for bone metastasis in non-small cell lung cancer based on serological characteristics of the bone metastasis mechanism

Bone metastasis significantly impact the prognosis of non-small cell lung cancer (NSCLC) patients, reducing their quality of life and shortening their survival. Currently, there are no effective tools for the diagnosis and risk assessment of early bone metastasis in NSCLC patients. This study employed machine learning to analyze serum indicators that are closely associated with bone metastasis, aiming to construct a model for the timely detection and prognostic evaluation of bone metastasis in NSCLC patients. The derivation cohort consisted of 664 individuals with stage IV NSCLC, diagnosed between 2015 and 2018. The variables considered in this study included age, sex, and 18 specific serum indicators that have been linked to the occurrence of bone metastasis in NSCLC. Variable selection used multivariate logistic regression analysis and Lasso regression analysis. Six machine learning methods were utilized to develop a bone metastasis diagnostic model, assessed with Area Under the Curve (AUC), Decision Curve Analysis (DCA), sensitivity, specificity, and validation cohorts. External validation used 113 NSCLC patients from the Medical Alliance (2019-2020). Furthermore, a prospective validation study was conducted on a cohort of 316 patients (2019-2020) who were devoid of bone metastasis, and followed-up for at least two years to assess the predictive capabilities of this model. The model's prognostic value was evaluated using Kaplan-Meier survival curves. Through variable selection, 11 serum indictors were identified as independent predictive factors for NSCLC bone metastasis. Six machine learning models were developed using age, sex, and these serum indicators. A random forest (RF) model demonstrated strong performance during the training and internal validation cohorts, achieving an AUC of 0.98 (95% CI 0.95-0.99) for internal validation. External validation further confirmed the RF model's effectiveness, yielding an AUC of 0.97 (95% CI 0.94-0.99). The calibration curves demonstrated a high level of concordance between the anticipated risk and the observed risk of the RF model. Prospective validation revealed that the RF model could predict the occurrence of bone metastasis approximately 10.27±3.58 months in advance, according to the results of the SPECT. An online computing platform (https://bonemetastasis.shinyapps.io/shiny_cls_1model/) for this RF model is publicly available and free-to-use by doctors and patients. This study innovatively employs age, gender, and 11 serological markers closely related to the mechanism of bone metastasis to construct an RF model, providing a reliable tool for the early screening and prognostic assessment of bone metastasis in NSCLC patients. However, as an exploratory study, the findings require further validation through large-scale, multicenter prospective studies. This work is supported by the National Natural Science Foundation of China (NO.81974315); Shanghai Municipal Science and Technology Commission Medical Innovation Research Project (NO.20Y11903300); Shanghai Municipal Health Commission Health Industry Clinical Research Youth Program (NO.20204Y034).

CT-based radiomics and clinical characteristics for predicting bone metastasis in lung adenocarcinoma patients.

The occurrence of bone metastasis (BM) will seriously shorten the survival time of lung adenocarcinoma patients and aggravate the suffering of patients. Computed tomography (CT)-based clinical radiomics nomogram may help clinicians stratify the risk of BM in lung adenocarcinoma patients, thereby enabling personalized individualized clinical decision making. A total of 501 patients with lung adenocarcinoma from March 2017 to March 2019 were enrolled in the study. Based on plain chest CT images, 1130 radiomics features were extracted from each lesion. One-way analysis of variance (ANOVA) and least absolute shrinkage selection operator (LASSO) algorithm were used for radiomics features selection. Univariate and multivariate analyses were used to screen for clinical characteristics and identify independent predictors of BM. Three models (radiomics model, clinical model and combined model) were constructed to predict BM in lung adenocarcinoma patients. Receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were used to evaluate the performance of the three models. The DeLong test was used to compare the performance of the models. Finally, the clinical model for predicting BM in lung adenocarcinoma patients was constructed based on 5 independent predictors: cytokeratin 19-fragments (CYFRA21-1), stage, Ki-67, edge, and lobulation. The radiomics model was constructed based on 5 radiomics features. The combined model incorporating clinical independent predictors and radiomics was constructed. In the validation cohort, the area under the curve (AUC) of the clinical model, radiomics model and combined model was 0.824, 0.842 and 0.866, respectively. Delong test showed that in the training cohort, the AUC values of the radiomics model and the combined model were statistically different (P=0.03), and the AUC values of the other models were not statistically different. DCA showed that the nomogram had a highest net clinical benefit. The CT-based clinical radiomics nomogram can be used as a non-invasive and quantitative method to help clinicians stratify the risk of BM in patients with lung adenocarcinoma, thereby enabling personalized clinical decision making.

Construction of a predictive model for bone metastasis from first primary lung adenocarcinoma within 3 cm based on machine learning algorithm: a retrospective study.

Adenocarcinoma, the most prevalent histological subtype of non-small cell lung cancer, is associated with a significantly higher likelihood of bone metastasis compared to other subtypes. The presence of bone metastasis has a profound adverse impact on patient prognosis. However, to date, there is a lack of accurate bone metastasis prediction models. As a result, this study aims to employ machine learning algorithms for predicting the risk of bone metastasis in patients. We collected a dataset comprising 19,454 cases of solitary, primary lung adenocarcinoma with pulmonary nodules measuring less than 3 cm. These cases were diagnosed between 2010 and 2015 and were sourced from the Surveillance, Epidemiology, and End Results (SEER) database. Utilizing clinical feature indicators, we developed predictive models using seven machine learning algorithms, namely extreme gradient boosting (XGBoost), logistic regression (LR), light gradient boosting machine (LightGBM), Adaptive Boosting (AdaBoost), Gaussian Naive Bayes (GNB), multilayer perceptron (MLP) and support vector machine (SVM). The results demonstrated that XGBoost exhibited superior performance among the four algorithms (training set: AUC: 0.913; test set: AUC: 0.853). Furthermore, for convenient application, we created an online scoring system accessible at the following URL: https://www.xsmartanalysis.com/model/predict/?mid=731symbol=7Fr16wX56AR9Mk233917, which is based on the highest performing model. XGBoost proves to be an effective algorithm for predicting the occurrence of bone metastasis in patients with solitary, primary lung adenocarcinoma featuring pulmonary nodules below 3 cm in size. Moreover, its robust clinical applicability enhances its potential utility.

The emerging role of osteoclasts in the treatment of bone metastases: rationale and recent clinical evidence.

The occurrence of bone metastasis is a grave medical concern that substantially impacts the quality of life in patients with cancer. The precise mechanisms underlying bone metastasis remain unclear despite extensive research efforts, and efficacious therapeutic interventions are currently lacking. The ability of osteoclasts to degrade the bone matrix makes them a crucial factor in the development of bone metastasis. Osteoclasts are implicated in several aspects of bone metastasis, encompassing the formation of premetastatic microenvironment, suppression of the immune system, and reactivation of quiescent tumor cells. Contemporary clinical interventions targeting osteoclasts have proven effective in mitigating bone-related symptoms in patients with cancer. This review comprehensively analyzes the mechanistic involvement of osteoclasts in bone metastasis, delineates potential therapeutic targets associated with osteoclasts, and explores clinical evidence regarding interventions targeting osteoclasts.

Correlation of Serum Prostate Specific Antigen and Gleason Grade with Bone Metastases in Patients with Prostate Cancer; An Experience at a Tertiary Care Hospital

Background: Prostate cancer (PCa) is the second most frequent cancer in the world and its incidence in Asian countries is on the rise. A lot of research work has been done in the Western world for the better understanding and treatment of the disease but the Western data may not be relevant to the data from Asian countries. Objective: To find out the association of serum prostate-specific antigen level and Gleason grade to the incidence of positive bone scan disease in our prostate cancer patient population. Methods: A four-year retrospective study that comprised 32 Prostate cancer (PCa) patients who were seen at The Indus Hospital and Health Network (IHHN) from October 2017 to December 2021. Recorded data were serum PSA value, histopathological examination of prostate tissue, and bone scan results. Histopathological examination of PCa was confirmed on biopsy with well-documented Gleason grade groups and scores. Results: Thirty-two patients with prostate cancer with a median age of 72.5 years (68-76.7), median PSA was 74 (12.4-100) ng/mL, and median GS was 9 (7-9) were included. Patients were segregated into four groups following their serum PSA levels ranging from ≤10 ng/ml (n=7; 21.8%), >10-≤20 ng/ml (n=4; 12.5%), > 20-≤100 ng/ml (n=14; 43.7%) and >100 ng/ml (n=7; 21.8%). Levels of PSA showed a significant association with BM (p=0.002). Similarly, in cancers with low Gleason grade, no bone metastasis was found (p=0.02). Conclusion: Raised PSA and high Gleason grade are associated with increased occurrence of bone metastasis in patients with carcinoma of the prostate and can be used as predictors of disease severity and progression.

Retracted: Observation of the Curative Effect of Acupuncture for Tonifying Kidney and Removing Blood Stasis Combined with Radiofrequency Surgery in Patients with NSCLC and the Diagnostic Efficacy of Combined Detection of NTx, BGP, and CYFRA21-1 in the Occurrence of Bone Metastases.

[This retracts the article DOI: 10.1155/2022/8157157.].

Influencing Factors of Bone Metastasis in Human Epidermal Growth Factor Receptor 2 Negative Breast Cancer and Efficacy of Capecitabine Plus Docetaxel

The clinical data characteristics of human epidermal growth factor receptor 2 negative breast cancer patients were analyzed to investigate the influencing factors of bone metastasis. A total of 754 patients with human epidermal growth factor receptor 2 negative breast cancer admitted to the First People's Hospital of Lianyungang from January 2017 to September 2022, including 273 patients in the bone metastasis group and 481 patients in the non-bone metastasis group, were retrospectively and systematically evaluated for their clinic pathological characteristics, treatment modalities and their influencing factors. Chi-square test and Mann-Whitney U test were used to calculate the differences in clinical data between patients with human epidermal growth factor receptor 2 negative bone metastases and those without bone metastases. Binary logistic regression was performed to analyses the risk factors for the development of bone metastases in human epidermal growth factor receptor 2 negative breast cancer. A significant difference was found between the patients in the bone metastasis group and the non-bone metastasis group in terms of T-stage, N-stage, estrogen receptor, progesterone receptor, tumour molecular classification, axillary lymph node metastasis and quality of life scores (functional assessment of cancer therapy-breast) after combined therapy with capecitabine plus docetaxel (Z=-2.706, Z=-2.864, χ2=75.954, χ2=55.618, χ2=114.854, χ2=305.211, χ2=66.945 and p<0.05), while statistical significance was absent in terms of age and location of the primary site (χ2=2.888, χ2=1.903 and p>0.05). Logistic regression analysis revealed that high T-stage, luminal A molecular staging and the occurrence of axillary lymph node metastases were all risk factors for bone metastases in human epidermal growth factor receptor 2 negative breast cancer patients (OR=4.352, 95 % CI=2.147 to 8.823, p<0.001; OR=0.281, 95 % CI=0.179 to 0.441, p<0.001 and OR=12.766, 95 % CI=6.712 to 24.283, p<0.001). The occurrence of bone metastases in human epidermal growth factor receptor 2 negative breast cancers was statistically correlated with T-stage, N-stage, estrogen receptor, progesterone receptor, molecular tumour staging, axillary lymph node metastasis and patient quality of life scores after combined therapy with capecitabine plus docetaxel. High T-stage, luminal A and axillary lymph node metastasis were all risk factors. Combined therapy of capecitabine and docetaxel provides significant efficacy in patients with human epidermal growth factor receptor 2 negative breast cancer bone metastases.

252P Real-world progression-free survival (rwPFS) and time to next line of therapy (TTNT) as intermediate endpoints for survival in metastatic breast cancer: A real-world experience

Real-world progression-free survival (rwPFS) and time to next line of therapy (TTNT) are two endpoints of clinical interest in patients with metastatic breast cancer (MBC). Their validation as intermediate endpoints for overall survival (OS), in a real-world setting, remains not fully established. We conducted a retrospective cohort study using the nationwide US Electronic Health Record-derived de-identified Flatiron Health database. The study population included pts diagnosed with MBC from Jan 1, 2011 through Feb 30, 2021. Kendall tau correlation between each surrogate endpoint (rwPFS and TTNT) and OS was evaluated using the Hougaard copula model. Kendall’s tau (τ) was calculated in the full cohort, and within each subgroup of metastatic disease, based on their prognostic significance, as defined by the occurrence of bone metastases (mets) only (subgroup 1), non-hepatic visceral mets +/- bone mets (subgroup 2), liver mets +/- other visceral and/or bone mets (subgroup 3), and one or more brain mets +/- other types of metastasis (subgroup 4). This work was supported by the imCORE network. Overall, 9,733 patients with MBC were included. Median age was 63 years (IQR: 54-72). Regarding sites of metastatic disease, subgroup 2 was most highly represented (n=4,188; 43.0%), followed by subgroup 1 (n=2,601; 26.7%), subgroup 3 (n=2,306; 23.7%) and subgroup 4 (n=638; 6.6%). Median OS in the overall population was 32.4 mos (95%CI: 31.2-33.3). Median rwPFS was 11.5 mos (95%CI: 11.1-11.9), and median TTNT was 11.1 mos (95%CI: 10.7-11.5). In the full cohort, the correlation of rwPFS with OS was 0.54, while that of TTNT with OS was 0.47 (Table).Table: 252PMedian OS, rwPFS and TTNT and Kendall tau correlation of each pair of evaluated endpoints.Overall Population (n=9,733)Subgroup 1 (n=2,601)Subgroup 2 (n=4,188)Subgroup 3 (n=2,306)Subgroup 4 (n=638)Median OS, months (95%CI)32.4 (31.2-33.3)44.3 (42.2-46.9)32.7 (31.0-34.0)22.6 (21.3-24.4)16.6 (14.8-19.7)Median rwPFS, months (95%CI)11.5 (11.1-11.9)18.5 (16.9-19.4)11.9 (11.4-12.7)8.2 (7.7-8.9)5.9 (4.9-6.7)Median TTNT, months (95%CI)11.1 (10.7-11.5)16.2 (15.1-17.9)11.3 (10.6-12.0)8.7 (8.2-9.2)6.7 (5.7-7.6)rwPFS-OS Correlation: τ (95%CI)0.54 (0.53-0.56)0.47 (0.45-0.50)0.54 (0.52-0.56)0.57 (0.55-0.59)0.60 (0.56-0.64)TTNT-OS Correlation: τ (95%CI)0.47 (0.46-0.48)0.37 (0.34-0.40)0.45 (0.43-0.46)0.54 (0.52-0.56)0.58 (0.55-0.62) Open table in a new tab Real-world PFS (rwPFS) and TTNT may represent meaningful intermediate endpoints for OS in patients with MBC overall, and within different disease subgroups.

A Nomogram for Predicting the Risk of Bone Metastasis in Newly Diagnosed Head and Neck Cancer Patients: A Real-World Data Retrospective Cohort Study From SEER Database.

Background: Bone metastasis (BM) is one of the typical metastatic types of head and neck cancer (HNC). The occurrence of BM prevents the HNC patients from obtaining a long survival period. Early assessment of the possibility of BM could bring more therapy options for HNC patients, as well as a longer overall survival time. This study aims to identify independent BM risk factors and develop a diagnostic nomogram to predict BM risk in HNC patients. Methods: Patients diagnosed with HNC between 2010 and 2015 were retrospectively evaluated in the Surveillance, Epidemiology, and End Results (SEER) database, and then eligible patients were enrolled in our study. First, those patients were randomly assigned to training and validation sets in a 7:3 ratio. Second, univariate and multivariate logistic regression analyses were used to determine the HNC patients’ independent BM risk factors. Finally, the diagnostic nomogram’s risk prediction capacity and clinical application value were assessed using calibration curves, receiver operating characteristic (ROC), and decision curve analysis (DCA) curves. Results: 39,561 HNC patients were enrolled in the study, and they were randomly divided into two sets: training (n = 27,693) and validation (n = 11,868). According to multivariate logistic regression analysis, race, primary site, tumor grade, T stage, N stage, and distant metastases (brain, liver, and lung) were all independent risk predictors of BM in HNC patients. The diagnostic nomogram was created using the above independent risk factors and had a high predictive capacity. The training and validation sets’ area under the curves (AUC) were 0.893 and 0.850, respectively. The AUC values of independent risk predictors were all smaller than that of the constructed diagnostic nomogram. Meanwhile, the calibration curve and DCA also proved the reliability and accuracy of the diagnostic nomogram. Conclusion: The diagnostic nomogram can quickly assess the probability of BM in HNC patients, help doctors allocate medical resources more reasonably, and achieve personalized management, especially for HNC patients with a potentially high BM risk, thus acquiring better early education, early detection, and early diagnosis and treatment to maximize the benefits of patients.

Bone Scintigraphy Metastatic Patterns in Patient with Prostate Cancer at Ocean Road Cancer Institute

Objectives: Prostate cancer is the second most common malignancy in the world next to lung cancer and it is the leading cause of morbidity and mortality among men. The most common metastatic site in prostate cancer is the bone. This study is aiming at finding the pattern and frequency of bone metastasis among prostate cancer patients at Ocean Road Cancer Institute, Tanzania. Methods: This was a cross section retrospective hospital based descriptive study involving 139 patients with prostate cancer who were seen from June 2014 to June 2016 whose bone scan were reviewed. Results: Bone metastases were found in 77 patients (55.4%) The prevalence was higher in the age group between 60 and 79 (56.3%) however there was no statistical significance between age and occurrence of bone metastasis. Patient who had high PSA level and Gleason score had more occurrence of skeletal metastasis. Spine was the most common site for bone metastasis constituting 72 patients (51.8%) of all the patients followed by ribs metastasis (31.7%), Also it was shown that of the spine metastasis, lumbar spine was more frequent affected (48.2%) followed by thoracic and cervical spine (41.0% and 27.3% respectively) Conclusion: The prevalence of skeletal metastasis in patients with Prostate cancer at Ocean Road Cancer Institute was high (55.4%). The prevalence was higher in patients with PSA level more than 20 and those with Gleason score of more than 7. Spine was the commonest site for metastasis and of the spine, metastasis lumbar spine metastasis was most frequent site. Recommendations: It is recommended that bone scan should be done as baseline in patients with prostate cancer particularly those with PSA level more than 20ng/ml and Gleason score of more than seven.

The homogeneity and heterogeneity of occurrence, characteristics, and prognosis in hepatocellular carcinoma patients with synchronous and metachronous bone metastasis.

Purpose: Based on the one of the largest hepatocellular carcinoma (HCC) population with bone metastasis (BM) from the single center in Tianjin, China, the present study aimed to investigate the risk and survival of synchronous bone metastasis (sBM) and metachronous bone metastasis (mBM) in HCC, and to reveal characteristics and related factors of HCC patients with bone metastasis.Methods: HCC patients with bone metastasis between 2009 and 2017 from Tianjin Medical University Cancer Institute & Hospital, Tianjin, China, were involved. Chi-square test/ Fisher's exact test and Logistic regression were used to estimate the risk factors of bone metastasis in HCC. Kaplan-Meier method was used to estimate the survival of HCC patients, and the Log-rank test was used to analyze the survival of HCC patients. The prognostic factors of HCC patients with BM were identified via Kaplan-Meier method and multivariable COX regression model.Results: Among 4421 HCC patients, 128 patients with BM were identified. Of the 128 patients with BM, 77 patients (60.16%) were with sBM and 51 patients (39.84%) were with mBM. The incidence of sBM in HCC was 1.74% at initial diagnosis. The most common metastatic site of sBM was rib, followed by lumbar, thoracic, and sacral. The median latency time from HCC diagnosis to mBM was six months. The most common site of mBM was thoracic, followed by lumbar, sacral and rib. Alcohol-drinking history (P=0.027), numbers (P=0.023) and size (P=0.008) of intrahepatic tumor, lymph node metastasis (P<0.001), serum ALP (P=0.004) and HGB (P=0.004) level were found to be correlated with the occurrence of BM. The overall survival between non-BM and BM were statistically different (P=0.028).Conclusion: The incidence of sBM in HCC was 1.74% at initial diagnosis. The median latency time from HCC diagnosis to mBM was 6 months. The characteristics between occurrence and prognosis showed significant difference between sBM and mBM. Early identification of high-risk BM population was essential for the improvement of both quality of life and prognosis. The revealed related factors can potentially guide sBM and mBM identification and early diagnosis in HCC.

Observation of the Curative Effect of Acupuncture for Tonifying Kidney and Removing Blood Stasis Combined with Radiofrequency Surgery in Patients with NSCLC and the Diagnostic Efficacy of Combined Detection of NTx, BGP, and CYFRA21-1 in the Occurrence of Bone Metastases.

The curative effect observation of acupuncture for tonifying kidney and removing blood stasis combined with radiofrequency surgery in patients with non-small-cell lung carcinoma (NSCLC) and the diagnostic efficacy of combined detection of NTx, BGP, and CYFRA21-1 for bone metastases are investigated. 122 NSCLC patients admitted to our hospital from January 2019 to December 2021 are selected for the examination, and the two sets of patients are randomly divided into the study set and the control set using the random number table method, with 61 cases in each set. Patients in the control set are given CT-guided percutaneous radiofrequency ablation therapy, and patients in the study set are given a combination of acupuncture therapy for tonifying the kidney and removing blood stasis on the basis of the therapy of the control set. The experimental results show that for NSCLC patients, the application of kidney-tonifying and stasis-removing acupuncture therapy combined with radiofrequency surgery can notoriously enhance the clinical therapy effect and enhance the quality of life of patients, and the detection of NTx, BGP, and CYFRA21-1 indicators can effectively predict the prognosis.

Value of CT Radiomics and Clinical Features in Predicting Bone Metastases in Patients with NSCLC.

Objective To explore the CT radiomic features and clinical imaging features of the primary tumor in patients with nonsmall cell lung cancer (NSCLC) before treatment and their predictive value for the occurrence of bone metastases. Methods From June 2017 to June 2021, 195 patients with NSCLC who were pathologically diagnosed without any treatment in the Cancer Hospital Affiliated to Hainan Medical College were retrospectively analyzed, and they were divided into a bone metastasis group and a nonbone metastasis group. The relationship between clinical imaging features and bone metastasis in patients was analyzed by the t-test, rank sum test, and χ2 test. At the same time, ITK software was used to extract the radiomic characteristics of the primary tumor of the patients, and the patients were randomly divided into a training group and a validation group in a ratio of 7 : 3. The training model was validated in the validation group, and the performance of the model for predicting bone metastases in NSCLC patients was verified by the ROC curve, and a multivariate logistic regression prediction model was established based on the omics parameters extracted from the best prediction model combined with clinical image features. Results Seven features were screened from the primary tumor by LASSO to establish a model for predicting metastasis. The area under the curve was 0.82 and 0.73 in the training and validation sets. The best omics signature and univariate analysis suggested clinical imaging factors (P < 0.05) associated with bone metastases were included in multivariate binary logistic analysis to obtain clinical characteristics of the primary tumor such as gender (OR = 0.141, 95% CI: 0.022–0.919, P = 0.04), increased Cyfra21-1 (OR = 0.12, 95% CI: 0.018–0.782, P = 0.027), Fe content in blood (OR = 0.774, 95% CI: 0.626–0.958, P = 0.018), CT signs such as lesion homogeneity (OR = 0.052, 95% CI: 0.006–0.419, P = 0.006), pleural indentation sign (OR = 0.007, 95% CI: 0.001–0.696, P = 0.034), and omics characteristics glszm_Small Area High Gray Level Emphasis (OR = 0.016, 95% CI: 0.001–0.286, P = 0.005) were independent risk factors for bone metastasis in patients. Conclusion The prediction model established based on radiomics and clinical imaging features has high predictive performance for the occurrence of bone metastasis in NSCLC patients.

Mechanisms, Diagnosis and Treatment of Bone Metastases.

Bone and bone marrow are among the most frequent metastatic sites of cancer. The occurrence of bone metastasis is frequently associated with a dismal disease outcome. The prevention and therapy of bone metastases is a priority in the treatment of cancer patients. However, current therapeutic options for patients with bone metastatic disease are limited in efficacy and associated with increased morbidity. Therefore, most current therapies are mainly palliative in nature. A better understanding of the underlying molecular pathways of the bone metastatic process is warranted to develop novel, well-tolerated and more successful treatments for a significant improvement of patients’ quality of life and disease outcome. In this review, we provide comparative mechanistic insights into the bone metastatic process of various solid tumors, including pediatric cancers. We also highlight current and innovative approaches to biologically targeted therapy and immunotherapy. In particular, we discuss the role of the bone marrow microenvironment in the attraction, homing, dormancy and outgrowth of metastatic tumor cells and the ensuing therapeutic implications. Multiple signaling pathways have been described to contribute to metastatic spread to the bone of specific cancer entities, with most knowledge derived from the study of breast and prostate cancer. However, it is likely that similar mechanisms are involved in different types of cancer, including multiple myeloma, primary bone sarcomas and neuroblastoma. The metastatic rate-limiting interaction of tumor cells with the various cellular and noncellular components of the bone-marrow niche provides attractive therapeutic targets, which are already partially exploited by novel promising immunotherapies.

Enhancer RNA SLIT2 Inhibits Bone Metastasis of Breast Cancer Through Regulating P38 MAPK/c-Fos Signaling Pathway.

BackgroundBreast cancer (BRCA) is the most common cancer in women, while the bones are one of the most common sites of metastasis. Although new diagnostic methods or radiation or chemotherapies and targeted therapies have made huge advances, the occurrence of bone metastasis is also linked with poorer survival. Enhancer RNAs (eRNAs) have been demonstrated to participate in the progression of tumorigenesis and metastasis. However, the role of eRNAs in BRCA bone metastasis remains largely unclear.MethodGene expression profiling of 1,211 primary BRCA and 17 bone metastases samples were retrieved from The Cancer Genome Atlas (TCGA) database, and the significant prognostic eRNAs were identified by Cox regression and least absolute shrinkage and selection operator (LASSO) regression. The acceptable accuracy and discrimination of the nomogram were indicated by the receiver operating characteristic (ROC) and the calibration curves. Then target genes of eRNA, immune cell percentage by CIBERSORT analysis, immune genes by single-sample gene set enrichment analysis (ssGSEA), hallmark of cancer signaling pathway by gene set variation analysis (GSVA), and reverse phase protein array (RPPA) protein chip were used to build a co-expression regulation network and identified the key eRNAs in bone metastasis of BRCA. Finally, Cell Counting Kit-8 (CCK8) assay, cell cycle assay, and transwell assay were used to study changes in cell proliferation, migration, and invasiveness. Immunoprecipitation assay and Western blotting were used to test the interaction and the regulation signaling pathways.ResultsThe 27 hub eRNAs were selected, and a survival-related linear risk assessment model with a relatively high accuracy (area under curve (AUC): 0.726) was constructed. In addition, seven immune-related eRNAs (SLIT2, CLEC3B, LBPL1, FRY, RASGEF1B, DST, and ITIH5) as prognostic signatures for bone metastasis of BRCA were further confirmed by LASSO and multivariate Cox regression and CIBERSORT analysis. Finally, in vitro assay demonstrated that overexpression of SLIT2 reduced proliferation and metastasis in BRCA cells. Using high-throughput co-expression regulation network, we identified that SLIT2 may regulating P38 MAPK/c-Fos signaling pathway to promote the effects of metastasis.ConclusionBased on the co-expression network for bone metastasis of BRCA, we screened key eRNAs to explore a prognostic model in predicting the bone metastasis by bioinformatics analysis. Besides, we identified the potential regulatory signaling pathway of SLIT2 in BRCA bone metastasis, which provides a promising therapeutic strategy for metastasis of BRCA.

FP12.06 Solid Subtype Predicts Early Bone Metastases in Sensitive EGFR-Mutated Lung Adenocarcinoma Patients After Surgery

Bone metastasis (BM) is common and associated with poor prognosis in NSCLC patients. However, valid predictors of BM remain insufficient. Solid pattern has been reported as a predictive factor in disease progression in resected NSCLC patients. This study aimed to explore the relationship between solid subtype and BM in EGFR-mutated lung adenocarcinoma patients after surgery. Patients with completely resected lung adenocarcinoma and sensitive EGFR mutation were included in our study. Patients with solid pattern were divided into solid-present group while the rest were in solid-absent group. CT (for chest and brain) was performed every 2-3 months. Bone scan was done every 4-6 months. BM was confirmed if one of the following criteria were fulfilled: (1) clinical or pathological confirmation of lung cancer and diagnosis of BM according to bone biopsy; or (2) pathologically diagnosed as lung cancer and with BM images. All patients received EGFR-TKI as the first-line treatment for progression after operation. Bone disease-free survival (bDFS), DFS and OS were assessed in this study. bDFS was defined as the time span between surgery and BM diagnosis. From January 2007 to January 2017, 237 eligible patients were identified. Among them, 81 patients (34.2 %) were solid-present. BM was observed in 94 patients (39.7 %). Solid-present patients had significantly shorter bDFS than solid-absent patients (14 months vs. 27 months; P < 0.001). The difference was still significant in patients with BM as first-site (12.5 months vs. 16.5 months; P = 0.016) and non-first-site progression (16.5 months vs. 45.5 months; P < 0.001) after surgery (Figure 1). In survival analysis, solid-present group showed a significantly shortened DFS (15 months vs. 19 months; P < 0.001) and OS (47 months vs. 77 months; P = 0.001) (Figure 2).View Large Image Figure ViewerDownload Hi-res image Download (PPT) These findings suggested that solid pattern predicted poor prognosis and early BM occurrence.

MicroRNAs Possibly Involved in the Development of Bone Metastasis in Clear-Cell Renal Cell Carcinoma.

Simple SummaryBone metastases cause substantial morbidity and implicate worse clinical outcomes for clear-cell renal cell carcinoma patients. MicroRNAs are small RNA molecules that modulate gene translation and are involved in the development of cancer and metastasis. We identified six microRNAs that are potentially specifically involved in metastasis to bone, of which two seem protective and four implicate a higher risk. This aids further understanding of the process of metastasizing to bone. Furthermore, these microRNA hold potential for biomarkers or therapeutic targets.Bone metastasis in clear-cell renal cell carcinoma (ccRCC) leads to substantial morbidity through skeletal related adverse events and implicates worse clinical outcomes. MicroRNAs (miRNA) are small non-protein coding RNA molecules with important regulatory functions in cancer development and metastasis. In this retrospective analysis we present dysregulated miRNA in ccRCC, which are associated with bone metastasis. In particular, miR-23a-3p, miR-27a-3p, miR-20a-5p, and miR-335-3p specifically correlated with the earlier appearance of bone metastasis, compared to metastasis in other organs. In contrast, miR-30b-3p and miR-139-3p were correlated with less occurrence of bone metastasis. These miRNAs are potential biomarkers and attractive targets for miRNA inhibitors or mimics, which could lead to novel therapeutic possibilities for bone targeted treatment in metastatic ccRCC.

Primary cilia regulate gastric cancer-induced bone loss via cilia/Wnt/β-catenin signaling pathway.

Cancer-associated bone disease is a frequent occurrence in cancer patients and is associated with pain, bone fragility, loss, and fractures. However, whether primary or non-bone metastatic gastric cancer induces bone loss remains unclear. Here, we collected clinical evidence of bone loss by analyzing serum and X-rays of 25 non-bone metastatic gastric cancer patients. In addition, C57BL mice were injected with the human gastric cancer cell line HGC27 and its effect on bone mass was analyzed by Micro-CT, immunoblotting, and immunohistochemistry. Furthermore, the degree of the proliferation and osteogenic differentiation of mesenchymal stem cells (MSCs) co-cultured with HGC-27 or SGC-7901 cells was analyzed by colony-formation assay, alizarin red staining, immunofluorescence, qPCR, immunoblotting, and alkaline phosphatase activity assay. These indicated that gastric cancer could damage bone tissue before the occurrence of bone metastases. We also found that cilia formation of MSCs was increased in the presence of HGC27 cells, which was associated with abnormal activation of the Wnt/β-catenin pathway. Expression of DKK1 inhibited the Wnt/β-catenin signaling pathway and partially rescued osteogenic differentiation of MSCs. In summary, our results suggest that gastric cancer cells might cause bone damage prior to the occurrence of bone metastasis via cilia-dependent activation of the Wnt/β-catenin signaling pathway.

Prostate Adenocarcinoma with Brain Metastasis: A Surveillance, Epidemiology, and End Results Database Analysis 2010-2015.

BackgroundProstate adenocarcinoma rarely metastasize to the brain. The aim of this study was to understand the risk association and survival outcomes comparing prostate cancer with brain metastasis (group 1) with prostate cancer without brain metastasis (group 2) at the time of initial diagnosis.Material/MethodsWe searched the Surveillance, Epidemiology, and End Results (SEER) statewide cancer registries for all cases of stage IV prostate cancer adenocarcinoma diagnosed between 2010 and 2015. We used the Kaplan-Meier method and Cox regression to analyze survival outcomes and logistic regression to study the association between the presence of brain metastasis and potential risk variables. Exclusion criteria were the presence of neuroendocrine and small cell histology.ResultsThe study included 14 753 patients. Of these, 187 patients were in group 1 (with brain metastasis) and 14 566 were in group 2 (without brain metastasis). When comparing the metastases distribution at the time of initial presentation between group 1 and group 2, the occurrence of bone metastasis was similar in the 2 groups (87% vs 90%); however, liver metastasis (13% vs 4%) and lung metastasis (29% vs 7%) were significantly higher in group 1. We found a strong association between brain metastasis and visceral metastasis. There was no association between age, race, and grade and having brain metastasis.ConclusionsOur analysis shows that visceral metastasis is associated with a higher risk of brain metastasis. Presence of a visceral metastasis can be a useful parameter to consider early magnetic resonance imaging of the brain to facilitate diagnosis of asymptomatic brain metastasis.