Bone Metastases Research Articles

The role of Cabazitaxel in patients with castration-resistant and osseous metastases prostate cancer. A Hellenic Cooperative Oncology Group Phase II Study.: Cabazitaxel in mCRPC patients with osseous metastases

BackgroundCabazitaxel is an effective treatment in metastatic castration-resistant prostate cancer (mCRPC) patients previously exposed to docetaxel and novel hormonal treatments. Understanding the molecular biology of mCRPC disease and taking into account the several approved treatment options, biomarkers are needed to guide decision making including cabazitaxel treatment. MethodsCababone was a phase II translational study that attempted to identify predictors of cabazitaxel efficacy. mCRPC with documented bone metastases were enrolled prospectively and treated with cabazitaxel 25mg/m2 every three weeks. Prostate cancer biopsies, bone marrow aspirates and blood samples were collected for translational research. ResultsSixty patients were enrolled and 59 received treatment according to protocol. Six-month progression free survival (PFS) rate was 47% (95% CI: 33% - 59%) and 12-month Overall Survival (OS) rate was 70% (95% CI: 56% - 80%). Patients with reactive hematopoiesis had improved PFS and OS with cabazitaxel treatment. Mutations in HRR genes were detected in 7 patients. ConclusionsNo differences in cabazitaxel efficacy were noted according to mutational status of HRR genes analyzed. No new safety issues were detected. In conclusion, CabaBone confirmed efficacy of cabazitaxel in mCRPC patients including the subgroup of patients with HRR mutations. Reactive hematopoiesis in bone marrow biopsies was related to improved survival warranting further investigation of bone biomarkers as predictors of cabazitaxel efficacy. Micro-AbstactCabaBone is a phase II translational study that evaluated the role of bone microenvironment and HRR genes mutations in the efficacy of cabazitaxel in mCRPC patients with bone-only disease. Study confirmed efficacy of cabazitaxel in patients independent of the presence of HRR gene mutations. Reactive hematopoiesis in bone marrow was recognized as a possible predictive and prognostic biomarker of cabazitaxel efficacy.

Clinical Efficacy of Microwave Ablation Combined with Percutaneous Osteoplasty in the Treatment of Flat Bone Metastases.

Evaluating the clinical efficacy and safety of microwave ablation combined with percutaneous osteoplasty (MWA + PO group) versus percutaneous osteoplasty (PO group) for the treatment of flat bone metastases. Patients with flat bone metastases and intractable pain who underwent PO and/or MWA from January 2016 to January 2023 in our hospital were included, with 36 cases in the MWA+PO group and 21 cases in the PO group. Changes in the visual analog scale (VAS), Oswestry Disability Index (ODI), and quality of life assessment scale(QOL) were evaluated regularly. Postoperative complications and target lesion tumor treatment responses were also observed. The VAS and ODI in both the MWA+PO group and the PO group significantly decreased at 1week, 1 month, and 3 months postoperatively, The VAS and ODI in the MWA+PO group were lower than those in the PO group postoperatively. The QOL in both the MWA+PO group and the PO group significantly increased at 1week, 1 month, and 3 months postoperatively, with the QOL in the MWA+PO group being higher than that in the PO group postoperatively. According to the mRECIST criteria (target lesion tumor treatment response), the ORR in the MWA+PO group and PO group was 52.8% and 9.5%, respectively, while the DCR was 94.4% and 57.1%, respectively (P <0.001 and<0.001). Different degrees of bone cement extravasation were observed in both the PO group (38.1%) and MWA+PO group(19.4%)(χ²=2.38, P=0.12), but none of the patients developed clinical symptoms related to bone cement extravasation. The average cost of surgery was ¥10,480.43higher in the MWA+PO group than in the PO group. The MWA+PO treatment is more effective in relieving patients' local pain, improving local dysfunction, and enhancing quality of life, and can effectively improve target lesion tumor ORR and DCR, but it is also more costly.

Descriptive Analysis of CT Scan Findings in Breast Cancer Patients with Bone Metastases in Universitas Andalas Hospital Radiotherapy Installation

Background: Breast cancer is experiencing the most significant increase in cases among all cancers worldwide. Approximately 65% to 75 % of advanced breast cancer patients will experience bone metastases. CT scan is the most affordable and accessible method for evaluating bone metastases. This study aims to describe the characteristics of CT scan examination of bone metastases in breast cancer patients in the radiotherapy installation at Universitas Andalas Hospital from 2019 until 2021. Methods: A total of 51 patients with breast cancer who had bone metastases were included in this quantitative descriptive study, using a total sampling approach. The clinical data was taken from the medical records at the radiotherapy installation at Andalas University Hospital. The collected data was processed and analyzed using SPSS statistical software. Results: Based on the results, the mean age of patients was 49 years. The most histopathological type was invasive carcinoma mammae of no special type (57%). The most common site for bone metastases is osteo vertebrae (35%). Mixed lesions were the most frequent bone metastatic finding (51%), with fractures occurring in 27% of cases. Conclusions: The results of this study are breast cancer with bone metastases occurring on average at the age of 49 years, histopathological type the most is invasive carcinoma mammae of no special type. Breast cancer with bone metastases is most common in Osteo Vertebrae with mixed lesions as well as pathological fracture with a low percentage.

Serum Inflammatory Dynamics as Novel Biomarkers for Immune Checkpoint Inhibitors in Non-small-cell Lung Cancer With Bone Metastases.

The aim of the study was to develop a novel predictive scoring system based on the dynamics of serum inflammatory indicators in immune checkpoint inhibitor (ICI) treatment on non-small-cell lung cancer (NSCLC) with bone metastases. Sixty patients with NSCLC and bone metastases treated with ICIs between January 2016 and March 2021 were included in the development cohort. Serum neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) levels were assessed before (pre-value) and 6 weeks after (post-value) ICI treatment, and a novel predictive score was developed: pre-value ≥ post-value, 0 points; pre-value < post-value, 1 point; total score: 0-2 points. The associations of these dynamics and the score with clinical outcomes, including overall survival (OS), progression-free survival (PFS), response rate (RR) of bone metastases, and disease control rate (DCR), were evaluated. Furthermore, cross-validation was performed with 23 patients after April 2021 using the same inclusion criteria. The patients with decreased serum inflammation levels had significantly better OS, PFS, and RR than those with increased levels. Applying the developed score to the development cohort, the patients with 0 points had significantly better OS, PFS, and RR than others. In multivariable analysis, the score independently predicted treatment response to ICI for bone metastasis and prognosis. Cross-validation showed that OS, PFS, and RR were significantly better in the patients in the 0-point group. The early NLR and CRP dynamics were associated with therapeutic responses to ICIs in NSCLC with bone metastases. Our novel scoring system based on these dynamics is simple and has a high predictive accuracy.

The Role of Biphosphonate and Denosumab in Bone Metastasis

Metastasis is a major contributor to cancer-related morbidity and mortality. Bone metastasis is prevalent and associated with pain and fractures, particularly in breast cancer where up to 80% of patients may be affected. Bisphosphonates, traditional anti-resorptive drugs, have been crucial in managing bone metastatic cancers. This article reviews the pathophysiology of bone metastasis, focusing on the invasion-metastasis cascade and the role of matrix metalloproteinases (MMPs). The formation of metastatic tissue in bones involves disrupting the balance of the bone remodeling process. The study delves into the three generations of bisphosphonates, elucidating their structural differences and mechanisms of action. First-generation bisphosphonates, such as etidronate and clodronate, lack nitrogen and interfere with cellular processes. Second-generation bisphosphonates, including alendronate and pamidronate, bind to nitrogen and inhibit farnesyl pyrophosphate synthase (FPPS) in the mevalonate pathway. Third-generation bisphosphonates like risedronate and zoledronate have a heterogeneous nitrogenous chain, enhancing anti-resorptive activity. Denosumab's distinct pharmacokinetics and potential risks upon discontinuation are discussed. The article emphasizes the need for clinicians to be vigilant about potential adverse effects, especially kidney toxicity with bisphosphonates, and to tailor treatment based on individual patient characteristics.

Current principles of hybrid imaging of breast cancer: a review of the literature

Background. Breast cancer is a major global public health problem and is the most common malignancy affecting women. Bone metastases are a common complication of advanced breast cancer, with nearly 65% of patients developing bone metastases. The presence of bone metastases can cause severe morbidity and mortality, as well as impair quality of life and increase the risk of skeletal damage. Accuratedetection and reliable assessment of therapeutic responses to bone metastases are imperative to inform treatment decisions, preserve quality of life, and ultimately improve overall survival. Thus, early identification of bone metastases is essential for effective treatment strategies and improved patient outcomes. Purpose – describe the modern principles and capabilities of hybrid imaging used for diagnosis, staging and follow-up of breast tumors. Illustrations are provided to better summarize and demonstrate the main concepts. Materials and methods. The analysis of full-text publications, which were selected through a literature search in foreign databases (PubMed, Scopus, ScienceDirectElsevier) for the period 2019–2023, was carried out. Results and discussion. During the analytical review of the literature, the experience of using modern methods of diagnosing breast tumors in Ukraine and abroad was analyzed. The selection of radiopharmaceutical drugs and tracers is considered. It has been established that the use of hybrid PET/CT and PET/MRI is the most promising imaging modality for the evaluation of breast cancer, providing a fully integrated morphological and functional imaging assessment. Conclusions. Hybrid imaging plays a key role in the diagnosis, staging, treatment selection, and follow-up of breast tumors. Awareness of this disease can reduce delay in diagnosis and facilitate interdisciplinary expert care.

Prognostic impact of body mass index on metastatic HER2-positive breast cancer survival

Background. The association between body mass index and prognosis in patients with HER2-positive metastatic breast cancer (mBC) is unclear. Purpose – the first purpose of our study was to determine whether BMI is an independent prognostic factor for progression-free survival (PFS) and overall survival (OS) in HER2-positive mBC patients. The second objective was to assess the mutual impact of baseline clinicopathological characteristics on survival outcomes. Materials and Methods. The study group included patients treated at the Sumy Regional Clinical Oncology Center. We considered the underweight patients if their BMI was &lt;18.5 kg/m2, normal weight 18.5–24.9 kg/m2, overweight 25.0–29.9 kg/m2, and obese ≥ 30 kg/m2. The following formula was used for calculations: weight/height2 (kilograms/meter2). Information about the height, weight, and other clinicopathological characteristics of the patient at the time of the start of drug therapy was taken from the primary medical documentation. Pearson’s test and Chi2 test for categorical variables were used to compare baseline clinicopathological characteristics in groups with normal, overweight, and obesity. The Kaplan-Meier method was used to establish the medians of PFS and OS. Cox regression analysis assessed the mutual impact on the survival of various clinicopathological characteristics. The statistical significance threshold was considered P ≤0.05. Results. Seventy-eight patients with HER2-positive mBC were enrolled and categorized according to their BMI in normal weight, overweight, and obese groups. BMI had a different impact on PFS and OS. Median PFS was 14.9, 11.9, and 14.2 months for normal-weight, overweight, and obese patients, respectively. There is no statistically significant difference in PFS between groups (Р = 0.110). Multivariable regression analysis confirmed no impact of BMI on PFS. Nevertheless, metastases in bones and kidneys and the nuclear grade were statistically significant determinants of PFS. Median OS was 26.4, 28.8, and 37.9 months for normal-weight, overweight, and obese patients, respectively. BMI, kidney metastases, and nuclear grade were prognostically significant determinants of OS. Conclusions. BMI is an independent prognostic factor of OS in patients with HER2-positive mBC. Obesity is associated with better OS but does not impact PFS. Metastases in bones and kidneys and the nuclear grade can predict survival outcomes.

Lymph nodes rather than pleural metabolic activity in 18F-FDG PET/CT correlates with malignant pleural effusion recurrence in advanced non-small cell lung cancer.

Frequently recurrent malignant pleural effusion (MPE) significantly hampers the life quality of advanced non-small cell lung cancer (NSCLC) patients. We aimed to explore the effects of progression patterns and local intervention on MPE recurrence and apply fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) to establish a predictive model for MPE recurrence in NSCLC. We retrospectively recruited two cohorts of patients including treatment-naïve NSCLC diagnosed with MPE at the onset and receiving PET/CT scanning, as well as those with MPE and undergoing first-line epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) treatment. Pleural maximum standardized uptake value (SUVmax), metabolic tumor burden (MTV), total lesion glycolysis (TLG), and uptake patterns as well as SUVmax of lymph nodes (LN) were extracted. The primary outcome was MPE recurrence defined as re-accumulation of cytologically proven ipsilateral MPE. Step-wise multivariate Cox regression was used to identify candidate variables. Cox regression analysis and random survival forest were applied to establish models. A total of 148 treatment-naïve patients with EGFR-TKI treatment and MPE were recruited during the median follow-up period of 683 days, with 69 (46.6%) and 35 (23.6%) witnessing MPE recurrence at least once and twice. Intrapleural perfusion therapy at first recurrence was a protective factor for the second MPE recurrence (P=0.006), while intrapleural perfusion therapy at baseline could not benefit the first MPE recurrence (P=0.14). Conversely, prior systemic progression indicative of the change of systemic treatment was a protective factor for time to the first MPE recurrence (P<0.001); instead, the change of systemic treatment at the first MPE recurrence was not associated with second MPE recurrence (P=0.53). In another cohort with treatment-naïve NSCLC patients with MPE and PET/CT scanning, 103 patients regardless of the actionable mutation status were recruited during the median follow-up period of 304 days. Multivariate analysis suggested that the LN SUVmax >4.50 g/mL [hazard ratio (HR), 2.54; P=0.01], female gender (HR, 0.40; P=0.01), bone metastases (HR, 3.16; P=0.001), and systemic treatment (targeted therapy vs. chemotherapy: HR, 0.32; P=0.002; immunotherapy therapy vs. chemotherapy: HR, 0.99; P=0.97) could collectively indicate MPE recurrence with an optimal 300-day area under the curve (AUC) of 0.83. For patients with actionable mutation, LN SUVmax >4.50 g/mL (P=0.02) could forecast MPE recurrence independently. In summary, LN rather than pleural metabolic activity or uptake patterns could predict MPE recurrence for patients with or without targeted therapy. We should re-consider the application of intrapleural perfusion treatment for first-onset MPE and prompt it more at the moment of recurrent MPE. Promisingly, we could probably apply the non-invasive tool to identify the risk factors for MPE recurrence.

The Role of Metastasectomy in Patients with Liver-Only Metastases from Gastric Adenocarcinoma.

The role of metastasectomy in patients with liver-only metastases from gastric adenocarcinoma remains under investigation. Therefore, we performed a national registry analysis comparing surgical treatment options for patients with gastric adenocarcinoma and liver-only metastases. In this retrospective National Cancer Database (2010-2019) study, adults (≥ 18 years) with gastric adenocarcinoma and liver-only metastases (no brain, bone, or lung metastases) were included. Patients were stratified into four groups: no surgical treatment, primary tumor resection (PTR), liver metastasectomy, and PTR with liver metastasectomy. Survival was evaluated using the Kaplan-Meier method, log-rank test, and Cox regression. Of 10,977 included patients, 93.6% underwent no surgical treatment, 4.6% PTR alone, 0.8% liver metastasectomy alone, and 1.0% both PTR and liver metastasectomy. The median OS after no surgical treatment was 6.5 months, after PTR alone 10.9 months, after liver metastasectomy alone 9.9 months, and after PTR and liver metastasectomy 18.6 months. In multivariable analysis, when adjusting for age, sex, race/ethnicity, insurance status, Charlson-Deyo score, chemotherapy, and radiation, PTR and liver metastasectomy was associated with superior OS compared with no surgical treatment (HR 2.17, 95% CI 1.76-2.69, p < 0.001), PTR alone (HR 1.42, 95% CI 1.12-1.79, p = 0.003), and liver metastasectomy alone (HR 1.96, 95% CI 1.45-2.64, p < 0.001). These data suggest that, in highly selected patients with gastric adenocarcinoma and synchronous liver-only metastases and favorable biology, surgical resection might grant a survival advantage.

Efficacy of a single 5mg zoledronic acid infusion in preventing bone loss and fracture in postmenopausal women with breast cancer.

Chemotherapy-induced bone loss (CTIBL) is common among breast cancer patients, requiring comprehensive assessment and intervention. Zoledronic acid, a strong inhibitor of bone resorption, is effective in CTIBL management, though information on dosing and intervals, particularly the efficacy of the 5mg annual dose for osteoporosis in breast cancer patients, is limited. In this 12-month prospective observational study, 85 breast cancer patients were divided into three groups: 17 received no treatment, 17 received tamoxifen, and 51 received anastrozole or letrozole (AI). Post-surgery, patients were administered a single 5mg dose of zoledronic acid and monitored over 12months for changes in bone mineral density (BMD), fracture rates, and biochemical markers. Initially, the AI group was the oldest, averaging 59.1 ± 8.7years. At baseline, no significant differences in variables, except age, were observed. After 12months, BMD increased in all groups following a single zoledronic acid dose, with the smallest increase in the AI group at the lumbar spine: no treatment (2.4% ± 6.1%), tamoxifen (2.6% ± 3.4%), AI (0.6% ± 14.5%) (p = 0.778). CTx and P1NP levels were consistently suppressed up to 12months post-treatment, with smaller reductions in the AI group. There were no significant differences in fracture or bone metastasis rates among groups. A single infusion of 5mg zoledronic acid was effective in increasing bone density in breast cancer patients. However, AI-treated patients showed less improvement in vertebral bone mineral density and biochemical markers. Further long-term studies with larger cohorts are needed.

Epidural Analgesia for Palliative Pain Management for A Patient with An Advanced Stage Prostate Cancer: A Case Report

Introduction: Patients with advanced-stage cancer should be able to stay at home with their families without suffering from pain. This case report aims to discuss challenges in pain management of a patient with bone metastasis of prostate cancer who received epidural analgesia at home. Challenges were related to the patients, health professionals, and system. Understanding each factor will bring insights to develop a workable pain management program in the palliative setting. Case Presentation: A 66-year-old male was diagnosed with left sacroiliac joint pain due to metastatic prostate cancer. After a three-year history of prostate cancer and ineffective chemotherapy, the patient complained of pain in the left hip that did not improve with conventional medications (paracetamol, tramadol, and Morphine Sustained Release/MST). In response, the consideration of an epidural implant emerged as a potential solution, offering the prospect of home-based care and autonomous medication administration through an epidural continuous block with intermittent drug injection. Conclusions: This case highlights home-based interventional pain management for cancer, addressing challenges at the patient, health professional, and system level. Overcoming these challenges requires a multidisciplinary approach and robust institutional policies. The insights gained offer valuable lessons for hospitals aiming to enhance the competence of pain and palliative care teams and establish comprehensive support systems in hospital and home settings.

Single-Cell Analysis of Bone-Marrow-Disseminated Tumour Cells

Metastasis frequently targets bones, where cancer cells from the primary tumour migrate to the bone marrow, initiating new tumour growth. Not only is bone the most common site for metastasis, but it also often marks the first site of metastatic recurrence. Despite causing over 90% of cancer-related deaths, effective treatments for bone metastasis are lacking, with current approaches mainly focusing on palliative care. Circulating tumour cells (CTCs) are pivotal in metastasis, originating from primary tumours and circulating in the bloodstream. They facilitate metastasis through molecular interactions with the bone marrow environment, involving direct cell-to-cell contacts and signalling molecules. CTCs infiltrate the bone marrow, transforming into disseminated tumour cells (DTCs). While some DTCs remain dormant, others become activated, leading to metastatic growth. The presence of DTCs in the bone marrow strongly correlates with future bone and visceral metastases. Research on CTCs in peripheral blood has shed light on their release mechanisms, yet investigations into bone marrow DTCs have been limited. Challenges include the invasiveness of bone marrow aspiration and the rarity of DTCs, complicating their isolation. However, advancements in single-cell analysis have facilitated insights into these elusive cells. This review will summarize recent advancements in understanding bone marrow DTCs using single-cell analysis techniques.

Distant metastasis patterns among lung cancer subtypes and impact of primary tumor resection on survival in metastatic lung cancer using SEER database.

This research aimed to systematically uncover the metastatic characteristics and survival rates of lung cancer subtypes and to evaluate the impact of surgery at the primary tumor site on cancer-specific survival in DM lung cancer. We used the Surveillance, Epidemiology, and End Results (SEER) database (2010-2019) to identify primary lung cancers with DM at presentation (M1). Kaplan-Meier (KM) survival curves were generated and compared utilizing log-rank tests. Cox regression methods were employed to determine hazard ratios (HR) and 95% confidence intervals related to CSS factors. Inverse probability of treatment weighting (IPTW) was applied to reduce bias. We analyzed 77,827 M1 lung cancer cases, with 41.22% having DM at presentation. Bone metastasis was most common in ADC, ASC, SCC, LCC; brain in LCNEC; liver in SCLC. Lung was common in TC + AC and SCC. Long-term survival was best in TC + AC and worst in SCLC (p < 0.001). Male gender, age < 50, primary tumor site (main bronchus, lower lobe), large tumor diameter, ADC/SCLC/SCC pathology, and regional lymph node involvement were significant risk factors for multiorgan metastasis. Age ≥ 50, male, large tumor diameter, positive lymph nodes, and multiorgan metastases were associated with lower CSS. In contrast, radiotherapy, chemotherapy, systemic therapy, and surgery were associated with higher CSS rates. Primary tumor resection improved survival in lung cancer patients (excluding small cell lung cancer, SCLC) with single organ metastases (KM log rank p < 0.001, HR = 0.6165; 95% CI (0.5468-0.6951)), especially in brain (p < 0.001, HR = 0.6467; 95% CI (0.5505-0.7596)) and bone (p = 0.182, HR = 0.6289; p < 0.01), but not in liver or intrapulmonary metastases after IPTW. Significant differences in DM patterns and corresponding survival rates exist among lung cancer subtypes. Primary tumor resection improves survival in lung cancer patients (excluding small cell lung cancer, SCLC) with single organ metastases, with better outcomes in patients with brain and bone metastases, while no significant benefit was seen in patients with liver and intrapulmonary metastases.

Pattern of Failure in Patients with Biochemical Recurrence After PSMA Radioguided Surgery.

Prostate-specific membrane antigen (PSMA)-targeted radioguided surgery (RGS) is evolving as a new treatment modality for patients with early biochemical recurrence of prostate cancer and disease limited to locoregional lymph nodes on PSMA-ligand PET/CT. Nevertheless, the pattern of failure (locoregional vs. systemic) after PSMA RGS remains unknown. Therefore, the aim of this retrospective analysis was to evaluate the pattern of disease using PSMA-ligand PET in patients experiencing relapse after PSMA RGS. Methods: We evaluated 100 patients with biochemical recurrence after previous PET-guided PSMA RGS who underwent PSMA-ligand PET (median prostate-specific antigen [PSA], 0.9 ng/mL; range, 0.2-14.2 ng/mL). All suspicious lesions for recurrent prostate cancer were grouped according to the molecular imaging TNM classification system. Detection rates and lesion localization were determined and stratified by PSA values and the International Society of Urological Pathology grade group. Further, lesion localization was compared before and after PSMA RGS. Results: The median time between PSMA RGS and PSMA-ligand PET for relapse was 11.4 mo (range, 5.5-25.6 mo). In total, 91 of 100 (91%) patients showed PSMA-ligand-positive findings. PSMA PET detection rates were 82.6%, 92.6%, 91.3%, and 96.3% for PSA levels of 0.2-0.49, 0.5-0.99, 1-1.99, and at least 2 ng/mL, respectively. More than half of the patients (53%; 48/91) showed local recurrence or pelvic lymph node metastases only. Extrapelvic lymph node metastases, bone metastases, and visceral metastases were present in 22% (20/91), 16% (15/91), and 9% (8/91) of the patients, respectively. With increasing International Society of Urological Pathology grade group, the percentage of patients with bone and visceral metastases increased, whereas the number of patients with only locoregional disease decreased. Conclusion: PSMA-ligand PET is a useful method to detect and localize recurrent disease in patients with biochemical failure after PSMA RGS, with more than half of the patients presenting with locoregional recurrence, offering the potential for a second local therapy (e.g., radiation therapy or repeated surgery).

AI diagnostics in bone oncology for predicting bone metastasis in lung cancer patients using DenseNet-264 deep learning model and radiomics

This study aims to predict bone metastasis in lung cancer patients using radiomics and deep learning. Early prediction of bone metastasis is crucial for timely intervention and personalized treatment plans. This can improve patient outcomes and quality of life. By integrating advanced imaging techniques with artificial intelligence, this study seeks to enhance predictive accuracy and clinical decision-making. MethodsWe included 189 lung cancer patients, comprising 89 with non-bone metastasis and 100 with confirmed bone metastasis. Radiomic features were extracted from CT images, and feature selection was performed using Minimum Redundancy Maximum Relevance (mRMR) and Least Absolute Shrinkage and Selection Operator (LASSO). We developed and validated a radiomics model and a deep learning model using DenseNet-264. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. Statistical comparisons were made using the DeLong test. ResultsThe radiomics model achieved an AUC of 0.815 on the training set and 0.778 on the validation set. The DenseNet-264 model demonstrated superior performance with an AUC of 0.990 on the training set and 0.971 on the validation set. The DeLong test confirmed that the AUC of the DenseNet-264 model was significantly higher than that of the radiomics model (p < 0.05). ConclusionsThe DenseNet-264 model significantly outperforms the radiomics model in predicting bone metastasis in lung cancer patients. The early and accurate prediction provided by the deep learning model can facilitate timely interventions and personalized treatment planning, potentially improving patient outcomes. Future studies should focus on validating these findings in larger, multi-center cohorts and integrating clinical data to further enhance predictive accuracy.

Development and validation of a prognostic nomogram for predicting liver metastasis in thyroid cancer: a study based on the surveillance, epidemiology, and end results database

This study aimed to create a prognostic nomogram to predict the risk of liver metastasis (LM) in thyroid cancer (TC) patients and assess survival outcomes for those with LM. Data were collected from the SEER database, covering TC patients from 2010 to 2020, totaling 110,039 individuals, including 142 with LM. Logistic regression and stepwise regression based on the Akaike information criterion (AIC) identified significant factors influencing LM occurrence: age, histological type, tumor size, bone metastasis, lung metastasis, and T stage (p < 0.05). A nomogram was constructed using these factors, achieving a Cindex of 0.977, with ROC curve analysis showing an area under the curve (AUC) of 0.977. For patients with TCLM, follicular TC, medullary TC, papillary TC, and examined regional nodes were associated with better prognosis (p < 0.001, HR < 1), while concurrent brain metastasis indicated poorer outcomes (HR = 2.747, p = 0.037). In conclusion, this nomogram effectively predicts LM risk and evaluates prognosis for TCLM patients, aiding clinicians in personalized treatment decisions

Prognostic Value of PlGF Upregulation in Prostate Cancer.

Prostate cancer (PCa) is the second most commonly diagnosed cancer in men worldwide, with metastasis, particularly to bone, being the primary cause of mortality. Currently, prognostic markers like PSA levels and Gleason classification are limited in predicting metastasis, emphasizing the need for novel clinical biomarkers. New molecules predicting tumor progression have been identified over time. Some, such as the immune checkpoint inhibitors (ICIs) PD-1/PD-L1, have become valid markers as theranostic tools essential for prognosis and drug target therapy. However, despite the success of ICIs as an anti-cancer therapy for solid tumors, their efficacy in treating bone metastases has mainly proven ineffective, suggesting intrinsic resistance to this therapy in the bone microenvironment. This study explores the potential of immunological intratumoral biomarkers, focusing on placental growth factor (PlGF), Vascular Endothelial Growth Factor Receptor 1 (VEGFR1), and Programmed Cell Death Protein 1 (PD-1), in predicting bone metastasis formation. we analyzed PCa samples from patients with and without metastasis by immunohistochemical analysis. Results revealed that PlGF expression is significantly higher in primary tumors of patients that developed metastasis within five years from the histological diagnosis. Additionally, PlGF expression correlates with increased VEGFR1 and PD-1 levels, as well as the presence of intratumoral M2 macrophages. These findings suggest that PlGF contributes to an immunosuppressive environment, thus favoring tumor progression and metastatic process. Results here highlight the potential of integrating these molecular markers with existing prognostic tools to enhance the accuracy of metastasis prediction in PCa. By identifying patients at risk for metastasis, clinicians can tailor treatment strategies more effectively, potentially improving survival outcomes and quality of life. This study underscores the importance of further research into the role of intratumoral biomarkers in PCa management.

Comparing the prognosis of esophageal adenocarcinoma with bone and liver metastases: A competing risk analysis.

About half of the patients with esophageal cancer are presenting with metastasis at initial diagnosis. However, few studies have concerned on the prognostic factors of metastatic esophageal adenocarcinoma (mEAC). This research aimed to investigate the effects of single bone metastasis (BM) and single liver metastasis (LM) on prognosis of mEAC patients. Data were obtained from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program database. We compared the effects of LM and BM on overall survival (OS), EAC-specific survival (CSS), and EAC-specific death (EASD) by multivariate Cox regression, Kaplan-Meier analysis, and competing risk regression models. A total of 1,278 EAC patients were recruited in this study. Of which 78.95% (1009/1278) were EASD, and 12.68% (162/1278) were non-EAC-specific death (non-EASD). In multivariate Cox regression analysis, surgery, chemotherapy, and AJCC.T2 (vs. T1) were identified as protective factors for OS&CSS, while divorced/separated, single/unmarried (vs. married), grade III-IV (vs. grade I-II) and BM (vs. LM) were identified as risk factors. Competing risk regression analysis further confirmed that surgery and chemotherapy were beneficial to the patients with mEAC, and BM (vs. LM) was a risk factor for mEAC patients when considering the existence of the competitive risk events. Our study indicated that mEAC patients with BM face a worse prognosis compared to those with LM. Additionally, surgery and chemotherapy emerge as protective factors for mEAC patients. These findings offer evidence-based insights for clinical management and contribute to the field.

TGF-β1 and FOXM1 siRNA co-loaded nanoparticles by disulfide crosslinked PEG-PDMAEMA for the treatment of triple-negative breast cancer and its bone metastases in vitro

Introduction Triple-negative breast cancer (TNBC) is characterized by higher malignancy and mortality and is prone to distant metastasis, among which bone is the most common site. It’s urgent to explore new strategies for the treatment of TNBC and its bone metastases. Methods A tumor environment responsive vector, poly-(dimethylaminoethyl methacrylate)-SS-poly(ethylene glycol)-SS-poly-(dimethylaminoethyl methacrylate) (PDMAEMA-SS-PEG-SS-PDMAEMA), was constructed to co-delivery transforming growth factor-β1 (TGF-β1) siRNA and forkhead box M1 (FOXM1) siRNA in MDA-MB-231 cells. The preparation, characterization, in vitro release, stability, and transfection efficiency of nanoparticles were measured. Cell viability, migration, and invasion of MDA-MB-231 cells were determined. Cell chemotactic migration and cell heterogeneity adhesion of MDA-MB-231 cells to the human osteoblast-like cell line MG-63 were determined. Results PDMAEMA-SS-PEG-SS-PDMAEMA self-assembled with siRNA at N/P of 15:1 into nanoparticles with a particle size of 122 nm. In vitro release exhibited redox and pH sensitivity, and the nanoparticles protected siRNA from degradation by RNase and serum protein, remaining stable at 4 °C with similar transfection efficiency with lipo2000. Nanoparticles co-loaded with TGF-β1 siRNA and FOXM1 siRNA inhibited the cell viability, migration and invasion of MDA-MB-231 cells, as well as chemotactic migration and heterogeneous adhesion of MDA-MB-231 cells to MG-63 cells, showing a synergetic effect. After gene silencing on TGF-β1 and FOXM1, the epithelial to mesenchymal transition (EMT) related molecules vimentin mRNA expression decreased while E-cadherin increased. Conclusions PDMAEMA-SS-PEG-SS-PDMAEMA was suitable for TGF-β1 siRNA and FOXM1 siRNA delivery, exhibiting a synergetic inhibition effect on TNBC and its bone metastases, which might be related to its synergetic inhibition on EMT.

Deep bone oncology Diagnostics: Computed tomography based Machine learning for detection of bone tumors from breast cancer metastasis

PurposeThe objective of this study is to develop a novel diagnostic tool using deep learning and radiomics to distinguish bone tumors on CT images as metastases from breast cancer. By providing a more accurate and reliable method for identifying metastatic bone tumors, this approach aims to significantly improve clinical decision-making and patient management in the context of breast cancer. MethodsThis study utilized CT images of bone tumors from 178 patients, including 78 cases of breast cancer bone metastases and 100 cases of non-breast cancer bone metastases. The dataset was processed using the Medical Image Segmentation via Self-distilling TransUNet (MISSU) model for automated segmentation. Radiomics features were extracted from the segmented tumor regions using the Pyradiomics library, capturing various aspects of tumor phenotype. Feature selection was conducted using LASSO regression to identify the most predictive features. The model’s performance was evaluated using ten-fold cross-validation, with metrics including accuracy, sensitivity, specificity, and the Dice similarity coefficient. ResultsThe developed radiomics model using the SVM algorithm achieved high discriminatory power, with an AUC of 0.936 on the training set and 0.953 on the test set. The model’s performance metrics demonstrated strong accuracy, sensitivity, and specificity. Specifically, the accuracy was 0.864 for the training set and 0.853 for the test set. Sensitivity values were 0.838 and 0.789 for the training and test sets, respectively, while specificity values were 0.896 and 0.933 for the training and test sets, respectively. These results indicate that the SVM model effectively distinguishes between bone metastases originating from breast cancer and other origins. Additionally, the average Dice similarity coefficient for the automated segmentation was 0.915, demonstrating a high level of agreement with manual segmentations. ConclusionThis study demonstrates the potential of combining CT-based radiomics and deep learning for the accurate detection of bone metastases from breast cancer. The high-performance metrics indicate that this approach can significantly enhance diagnostic accuracy, aiding in early detection and improving patient outcomes. Future research should focus on validating these findings on larger datasets, integrating the model into clinical workflows, and exploring its use in personalized treatment planning.