Journal of Bone Oncology最新文献

The establishment and progression of bone metastatic breast cancer is supported by immunosuppressive myeloid populations that enable tumor growth by dampening the innate and adaptive immune response. Much work remains to understand how to target these tumor-myeloid interactions to improve treatment outcomes. Noncanonical Hedgehog signaling is an essential component of bone metastatic tumor progression, and prior literature suggests a potential role for Hedgehog signaling and its downstream effector Gli2 in modulating immune responses. In this work, we sought to identify if inhibition of noncanonical Hedgehog signaling alters the cytokine profile of osteolytic breast cancer cells and the subsequent communication between the tumor cells and myeloid cells. Examination of large patient databases revealed significant relationships between Gli2 expression and expression of markers of myeloid maturation and activation as well as cytokine expression. We found that treatment with HPI-1 reduced tumor cell expression of numerous cytokine genes, including CSF1, CSF2, and CSF3, as well as CCL2 and IL6. Secreted CSF-1 (M−CSF) was also reduced by treatment. Changes in tumor-secreted factors resulted in polarization of THP-1 monocytes toward a proinflammatory phenotype, characterized by increased CD14 and CD40 surface marker expression. We therefore propose M−CSF as a novel target of Hedgehog inhibition with potential future applications in altering the immune microenvironment in addition to its known roles in reducing tumor-induced bone disease.

Purpose

This study aims to devise and assess an automated measurement framework for lumbar pedicle screw parameters leveraging preoperative computed tomography (CT) scans and a deep learning algorithm.

Methods

A deep learning model was constructed employing a dataset comprising 1410 axial preoperative CT images of lumbar pedicles sourced from 282 patients. The model was trained to predict several screw parameters, including the axial angle and width of pedicles, the length of pedicle screw paths, and the interpedicular distance. The mean values of these parameters, as determined by two radiologists and one spinal surgeon, served as the reference standard.

Results

The deep learning model achieved high agreement with the reference standard for the axial angle of the left pedicle (ICC = 0.92) and right pedicle (ICC = 0.93), as well as for the length of the left pedicle screw path (ICC = 0.82) and right pedicle (ICC = 0.87). Similarly, high agreement was observed for pedicle width (left ICC = 0.97, right ICC = 0.98) and interpedicular distance (ICC = 0.91). Overall, the model’s performance paralleled that of manual determination of lumbar pedicle screw parameters.

Conclusion

The developed deep learning-based model demonstrates proficiency in accurately identifying landmarks on preoperative CT scans and autonomously generating parameters relevant to lumbar pedicle screw placement. These findings suggest its potential to offer efficient and precise measurements for clinical applications.

Background

The Radiotherapy IBandronate (RIB) trial compared single dose radiotherapy and a single infusion of ibandronate in 470 bisphosphonate naïve patients with metastatic bone pain from prostate cancer randomised into a non-inferiority two arm study. Results for the primary endpoint of pain score response at 4 weeks showed that the ibandronate arm was non-inferior to single dose radiotherapy.

Patients and method

In addition to pain assessments including analgesic use made at baseline, 4, 8, 12, 26 and 52 weeks, urine was collected at baseline, 4 and 12 weeks. It was subsequently analysed for urinary N-telopeptide (NTx) and cystatin C. Linear regression models were used to compare the continuous outcome measures for urinary markers within treatment arms and baseline measurements were included as covariates. Interaction terms were fitted to allow for cross-treatment group comparisons.

Results

The primary endpoint of the RIB trial was worst pain response at 4 weeks and there was no treatment difference seen. Urine samples and paired pain scores at 4 weeks were available for 273 patients (radiotherapy 168; ibandronate 159)

The baseline samples measured for the RIB trial had an average concentration of 193 nM BCE/mM creatinine (range of 7.3–1871) compared to the quoted normal range of 33 nM BCE/mM creatinine (3 to 63). In contrast the average value of Cystatin C was 66 ng/ml (ranges ND – 1120 ng/ml) compared to the quoted normal range of 62.9 ng/ml (ranges 12.6–188 ng/ml). A statistically significant reduction in NTx concentrations between baseline and 4 weeks was seen in the ibandronate arm but not in the radiotherapy arm. No correlation between pain response and urinary marker concentration was seen in either the ibandronate or radiotherapy cohort at any time point.

Conclusion

NTx was significantly raised compared to the normal range consistent with a role as a biomarker for bone metastases from prostate cancer. A significant reduction in NTx 4 weeks after ibandronate is consistent with its action in osteoclast inhibition which was not seen after radiotherapy implying a different mode of action for radiation. There was no correlation between bone biomarker levels and pain response.

Background/purpose

This study aimed to summarize the survival and complication profiles of the compress® endoprosthesis (CPS) through a systematic review and meta-analysis.

Methods

Online databases (PubMed, EMBASE and Web of Science) were searched from inception to November 2023. Trials were included that involved the use of CPS for endoprosthetic replacement in patients with massive segmental bone defects. Patients’ clinical characteristics and demographic data were extracted using a standardized form. The methodological quality of included 13 non-comparative studies was assessed on basis of the Methodological Index for Non-Randomized Studies (MINORS). All the available Kaplan-Meier curves in the included studies were digitized and combined using Engauge-Digitizer software and the R Project for Statistical Computing.

Results

The meta-analysis of thirteen included studies indicated: the all-cause failure rates of CPS were 26.3 % after surgery, in which the occurrence rates of aseptic loosening were 5.8 %. And the incidences of other complications were as follows: soft tissue failure (1.8 %), structure failure (8.2 %), infection (9.5 %), tumor progression (1.1 %). The 1-, 4-, and 8-year overall survival rates for all-cause failure with 95 % CI were 89 % (86 %-92 %), 75 % (71 %-79 %) and 65 % (60 %-70 %), respectively. The estimated mean survival time of all-cause failure was 145 months (95 % CI, 127–148 months), and the estimated median survival time of all-cause failure was 187 months (95 % CI, 135–198 months). The 1-, 4-, and 8-year overall survival rates of aseptic loosening with 95 % CI were 96 % (94 %-98 %), 91 % (87 %-95 %) and 88 % (83 %-93 %), respectively. The estimated mean survival time of aseptic loosening was 148 months (95 % CI, 137–153 months).

Conclusion

CPS’s innovative spring system promotes bone ingrowth by providing immediate and high-compression fixation, thereby reducing the risk of aseptic loosening caused by stress shielding and particle-induced osteolysis. CPS requires less residual bone mass for reconstructing massive segmental bone defects and facilitates easier revision due to its non-cemented fixation. In addition, the survival rate, estimated mean survival time, and complication rates of CPS are not inferior to those of common endoprosthesis.

Objective

The main objective of this study was to create and assess a detailed diagnostic model with an optimizing feature selection algorithm that combines computed tomography (CT) imaging characteristics, demographic information, and genetic markers to enhance the accuracy of benign and malignant classification of osteosarcoma. This research seeks to enhance the early identification and categorization of benign and malignant of osteosarcoma, ultimately enabling more personalized and efficient treatment approaches.

Methods

Data from 225 patients diagnosed with osteosarcoma at two different medical institutions between June 2018 and June 2021 were gathered for this research study. A novel feature selection approach that combined Principal Component Analysis (PCA) with Improved Particle Swarm Optimization (IPSO) was utilized to analyze 1743 image-derived features. The performance of the resulting model was evaluated using metrics such as area under the receiver operating characteristic curve (AUC), accuracy (ACC), sensitivity (SEN), and specificity (SPE), and compared to models developed using conventional feature selection methods.

Results

The proposed model showed promising predictive performance with an AUC of 0.87, accuracy of 0.80, sensitivity of 0.75, and specificity of 0.85. These results suggest improved predictive ability compared to models built using traditional feature selection techniques, particularly in terms of accuracy and specificity. However, there is room for improvement in enhancing sensitivity.

Conclusion

Our study introduces a novel predictive model for distinguishing between benign and malignant osteosarcoma., emphasizing its potential significance in clinical practice. Through the utilization of CT imaging features, our model shows improved accuracy and specificity, marking progress in the early detection and classification of osteosarcoma as either benign or malignant. Future investigations will concentrate on enhancing the model’s sensitivity and validating its effectiveness on a larger dataset, aiming to boost its clinical relevance and support personalized treatment approaches for osteosarcoma.

Objectives

The present study evaluates the clinical outcomes of children, adolescents and adults with Ewing sarcoma and identifies the prognostic factors.

Methods

Included in the study were 222 pediatric and adult patients diagnosed with Ewing sarcoma (EwS) who were followed up between 1992 and 2019, and whose data were analyzed retrospectively.

Results

The median age of 131 male and 91 female patients included in the study was 13 (1–64). The median follow-up duration of the survivors was 79 months (range, 11–182 months). The 3-year EFS rate of the 222 patients was 34 % (Confidence Interval (CI) (0.158–0.242 %) and the OS rate was 54 % (CI, 0.289–0.590 %). For the non-metastatic patients, the 3-year EFS rate was 47 % and the OS was 68 %, while for the metastatic patients the 3-year EFS rate was 13 % and the OS was 30 %. Of the patient sample, 81 (36, 5 %) survived, of whom 72 were continuously free of disease while the disease persisted in nine, and three developed a secondary neoplasm (2 of whom subsequently died while one survived disease-free). Of the 129 patients who relapsed with metastases and/or local recurrence, eight survived and are disease-free, nine are alive with uncontrolled disease; five were lost to follow-up and 107 died.

Conclusion

The findings of the present study suggest metastatic disease at presentation and positive margins after surgery to be of prognostic significance in EwS. Disruptions in aggressive local treatments may reduce the chances of cure in EwS.

Therapy-related myeloid neoplasms (t-MN) are a growing concern due to the continued use of cytotoxic therapies to treat malignancies. Cytotoxic therapies have been shown to drive therapy-induced senescence in normal tissues, including in the bone marrow microenvironment (BMME), which plays a crucial role in supporting normal hematopoiesis. This review examines recent work that focuses on the contribution of BMME senescence to t-MN pathogenesis, as well as offers a perspective on potential opportunities for therapeutic intervention.

Osteosarcoma is the most common primary malignant bone tumor in adolescents. While treatments for osteosarcoma have improved, the overall survival has not changed for three decades, and thus, new targets for therapeutic development are needed. Recently, glucocorticoids have been reported to have antitumor effects. Mometasone furoate (MF), a synthetic glucocorticoid, is of great value in clinical application, but there are few reports on its antitumor effect. Here, we verified the effect of MF on osteosarcoma in vitro and in vivo. In vitro, cell proliferation, cell cycle progression, apoptosis and cell metastasis were detected using Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, wound-healing and transwell assays, respectively. In vivo, we generated a xenograft mouse model. To examine the potential role of the AMPK pathway, an AMPK-specific inhibitor (dorsomorphin) was used. The expression levels of factors related to the cell cycle, apoptosis and activation of the AMPK/mTOR pathway were assessed by immunohistochemistry and Western blotting. MF inhibited proliferation and metastasis and induced S phase arrest and apoptosis in osteosarcoma cells in a dose-dependent manner. In vivo, MF effectively inhibited osteosarcoma cell growth and pulmonary metastasis; however, it had no negative effect on the internal organs. Additionally, MF could activate the AMPK/mTOR pathway in osteosarcoma. Dorsomorphin significantly attenuated MF-induced antitumor activities. In summary, MF can inhibit osteosarcoma proliferation and metastasis and promote osteosarcoma cell apoptosis through the AMPK/mTOR signaling pathway in vitro and in vivo, which can provide a new rationale for subsequent academic and clinical research on osteosarcoma treatment.

Texture analysis can provide new imaging-based biomarkers. Texture analysis derived from computed tomography (CT) might be able to better characterize patients undergoing CT-guided percutaneous bone biopsy. The present study evaluated this and correlated texture features with bioptic outcome in patients undergoing CT-guided bone biopsy. Overall, 123 patients (89 female patients, 72.4 %) were included into the present study. All patients underwent CT-guided percutaneous bone biopsy with an 11 Gauge coaxial needle. Clinical parameters and quantitative imaging features were investigated. Random forest classifier was used to predict a positive biopsy result. Overall, 69 patients had osteolytic metastasis (56.1 %) and 54 had osteoblastic metastasis (43.9 %). The overall positive biopsy rate was 72 %. The developed radiomics model demonstrated a prediction accuracy of a positive biopsy result with an AUC of 0.75 [95 %CI 0.65 – 0.85]. In a subgroup of breast cancer patients, the model achieved an AUC of 0.85 [95 %CI 0.73 – 0.96]. In the subgroup of non-breast cancer patients, the signature achieved an AUC of 0.80 [95 %CI 0.60 – 0.99]. Quantitative CT imaging findings comprised of conventional and texture features can aid to predict the bioptic result of CT-guided bone biopsies. The developed radiomics signature aids in clinical decision-making, and could identify patients at risk for a negative biopsy.

Introduction

Androgen Deprivation Therapy (ADT) for prostate cancer (PC) has substantial negative impacts on the musculoskeletal system and body composition. Many studies have focused on the effects of ADT on areal bone mineral density (aBMD), but aBMD does not capture key determinants of bone strength and fracture risk, for example volumetric bone density (vBMD), geometry, cortical thickness and porosity, trabecular parameters and rate of remodelling. More specialist imaging techniques such as high-resolution peripheral quantitative computed tomography (HR-pQCT) have become available to evaluate these parameters. Although it has previously been demonstrated that bone microarchitectural deterioration occurs in men undergoing ADT, the aim of the ANTELOPE study was to examine longitudinal changes in bone microstructure alongside a range of musculoskeletal parameters and frailty, comparing men with PC receiving ADT alone or ADT plus chemotherapy for metastatic disease, with a healthy age-matched population.

Methods

We used HR-pQCT to investigate effects of 12 months of ADT on vBMD and microstructural parameters, complemented by assessment of changes in aBMD, serum bone turnover markers, sex hormones, body composition, grip strength, physical and muscle function, frailty and fracture risk. We studied three groups: Group A − men with localised/locally advanced PC due to commence ADT; Group B − men with newly diagnosed hormone-sensitive, metastatic PC, starting ADT alongside docetaxel chemotherapy and steroids; Group C − healthy, age-matched men. The primary endpoint was change in vBMD (Group A vs Group C) at the distal radius.

Results

Ninety-nine participants underwent baseline study assessments (Group A: n = 38, Group B: n = 30 and Group C: n = 31). Seventy-five participants completed all study assessments (Group A (29), Group B (18), Group C (28). At baseline, there were no significant differences between Groups A and C in any of the BMD or bone microstructure outcomes of interest. After 12 months of ADT treatment, there was a significantly greater decrease in vBMD (p < 0.001) in Group A (mean 12-month change = -13.7 mg HA/cm³, −4.1 %) compared to Group C (mean 12-month change = -1.3 mg HA/cm³, −0.4 %), demonstrating achievement of primary outcome. Similar effects were observed when comparing the change in vBMD between Group B (mean 12-month change = -13.5 mg HA/cm³, −4.3 %) and Group C. These changes were mirrored in aBMD. ADT resulted in microstructural deterioration, a reduction in estimated bone strength and an increase in bone turnover. There was evidence of increase in total fat mass and trunkal fat mass in ADT-treated patients, with marked loss in upper limb mass, along with BMI gain. Frailty increased and physical performance and strength deteriorated in both ADT groups, relative to the healthy control group.

Conclusion