Thermomechanical Virtual Simulation of Bone Metastases with Percutaneous Cementoplasty and Internal Fixation

Jiang W., Latich I., Lindskog D., Friedlaender G., Lee F.Y.

Intramedullary nailing insertion from the proximal-to-distal femur is frequently performed for impending and complete pathological femur fractures due to osteolytic metastases. After nailing through cancer-laden bone, residual chemotherapy- and/or radiation-resistant tumor may progress. Progression of osteolysis risks future nail failure or pathological fractures. This study assesses the incidence of cancer progression following intramedullary nailing in a femur-only cohort and describes a percutaneous rod-retaining salvage technique. A single-institution, retrospective study was conducted to identify adult patients who underwent intramedullary nailing for femoral osteolytic lesions for complete or impending nail failure from 2016 to 2023. Progression was defined as enlargement of the pre-existing lesion and/or appearance of new lesions on radiographs. Surgical outcomes were assessed with a combined pain and functional score. A total of 113 patients (median age 66.8 years (IQR = 16.4); median follow-up 6.0 months (IQR = 14.5)) underwent intramedullary nailing. Sixteen patients (14.2%) exhibited post-nailing cancer progression. Pre- and postoperative radiation and chemotherapy did not decrease the odds of cancer progression. Three patients underwent initial open surgical salvage consisting of proximal femur replacement arthroplasty, and six patients did not receive salvage due to poor surgical candidacy or patient choice. Seven patients (median follow-up 10.7 months (IQR = 12.9)) received percutaneous salvage. In this group, pain and functional scores improved by 4.0 points (p = 0.0078) at two-week postoperative follow-up and 2.0 points (p = 0.0312) at the most recent follow-up (mean follow-up 13.0 ± 9.4 months). All three nonambulatory patients became ambulatory, and six patients were able to ambulate independently without walking aids. No major complications were reported 30 days postoperatively. Progression of femoral osteolytic metastases may occur following intramedullary nailing. Continued monitoring of the entire femur is needed to maintain improved functional status and to prevent catastrophic progression of pre-existing lesions or appearance of new lesions. In patients with more proximal metastases only, the customary practice of bringing a long nail from the proximal femur to distal metaphysis should be reconsidered. Furthermore, there is concern of mechanical transport of cancer cells during guide wire insertion, reaming, and rod insertion through cancer laden bone to cancer free distal bone.

Tomas Batlle X., Soler-Perromat J.C., Blasco Andaluz J., Fernández-Valencia J.A.

Progressive population aging and improved healthcare have led to a significant increase in patients with hip arthroplasty (HA). In this patient group, the proportion of those who require a new arthroplasty (prosthetic replacement or secondary revision of the hip), has also increased. For this subgroup of patients in whom surgical prosthetic replacement should be considered but is contraindicated, a new technique has been developed since 2010: percutaneous injection of periprosthetic cement under fluoroscopic or CT control ("femoroplasty; FMP") as an alternative and less invasive treatment compared to surgery to stabilize the HA without replacing it, with excellent results on patients' quality of life. In this brief communication, we describe our positive experience regarding FMP, which we have performed for the first time in Spain on four patients (age range between 74-83 years, 2 female and 2 male patients, 3 right HA and 1 left HA), without post-complications. We highlight both the relative simplicity of this technique, which can be incorporated into radiological intervention even in regional hospitals, and the significant clinical improvement observed in all patients. In conclusion, we hope that our experience can contribute to the increased adoption of this innovative technique within the scientific community.

Bazyar P., Baumgart A., Altenbach H., Usbeck A.

Specific finite detail modeling of the human body gives a capable primary enhancement to the prediction of damage risk through automobile impact. Currently, car crash protection countermeasure improvement is based on an aggregate of testing with installed anthropomorphic test devices (i.e., ATD or dummy) and a mixture of multibody (dummy) and finite element detail (vehicle) modeling. If an incredibly easy finite element detail version can be advanced to capture extra statistics beyond the abilities of the multi-body structures, it might allow advanced countermeasure improvement through a more targeted prediction of overall performance. Numerous research has been done on finite element analysis of broken femurs. However, there are two missing pieces of information: 1- choosing the right material properties, and 2- designing a precise model including the inner structure of the bone. In this research, most of the chosen material properties for femur bone will be discussed and evaluated.

Castaneda M., den Hollander P., Kuburich N.A., Rosen J.M., Mani S.A.

Metastatic cancer is almost always terminal, and more than 90% of cancer deaths result from metastatic disease. Combating cancer metastasis and post-therapeutic recurrence successfully requires understanding each step of metastatic progression. This review describes the current state of knowledge of the etiology and mechanism of cancer progression from primary tumor growth to the formation of new tumors in other parts of the body. Open questions, avenues for future research, and therapeutic approaches with the potential to prevent or inhibit metastasis through personalization to each patient's mutation and/or immune profile are also highlighted.

Bensoussan S., Premat K., Shotar E., Cormier É., Raasi A.A., Spano J., Morardet L., Bonaccorsi R., Morel V., Mathout J., Chiras J., Clarençon F.

Characterizing orbital lesions remains challenging with imaging. The purpose of this study was to compare 3 Tesla (T) to 7 T magnetic resonance imaging (MRI) for characterizing orbital lesions.This prospective single-center study enrolled participants presenting with orbital lesions from May to October 2019, who underwent both 7 T and 3 T MRI examinations. Two neuroradiologists, blinded to all data, read both datasets independently and randomly. They assessed general characteristics of each orbital lesion as well as image quality and presence of artifacts. Comparison between both datasets was made using Fisher exact test.Seven patients (4 women, 3 men) with a median age of 52 years were enrolled. Orbital lesion conspicuity was better scored at 7 T compared to 3 T MRI, with 3/7 lesions (43%) scored as very conspicuous at 7 T compared to 0/7 lesion (0%) at 3 T, although the difference was not significant (P = 0.16). Delineation of lesion margins was better scored at 7 T compared to 3 T with 3/7 lesions (43%) scored as very well delineated on 7 T compared to 0/7 lesions (0%) at 3 T, although the difference was not significant (P = 0.34). Details of internal structure were better assessed at 7 T compared to 3 T, with 4/7 lesions (57%) displaying numerous internal details compared to 0/7 lesions (0%) at 3 T (P = 0.10). Internal microvessels were visible in 3/7 lesions (43%) at 7 T compared to 0/7 lesions (0%) at 3 T (P = 0.19).Although no significant differences were found between 7 T and 3 T MRI, assumably due to a limited number of patients, our study suggests that 7 Tesla MRI might help improve the characterization of orbital lesions. However, further studies with more patients are needed.

Papalexis N., Parmeggiani A., Peta G., Spinnato P., Miceli M., Facchini G.

Metastases are the main type of malignancy involving bone, which is the third most frequent site of metastatic carcinoma, after lung and liver. Skeletal-related events such as intractable pain, spinal cord compression, and pathologic fractures pose a serious burden on patients’ quality of life. For this reason, mini-invasive treatments for the management of bone metastases were developed with the goal of pain relief and functional status improvement. These techniques include embolization, thermal ablation, electrochemotherapy, cementoplasty, and MRI-guided high-intensity focused ultrasound. In order to achieve durable pain palliation and disease control, mini-invasive procedures are combined with chemotherapy, radiation therapy, surgery, or analgesics. The purpose of this review is to summarize the recently published literature regarding interventional radiology procedures in the treatment of cancer patients with bone metastases, focusing on the efficacy, complications, local disease control and recurrence rate.

Li C., Wu Q., Chang D., Liang H., Ding X., Lao C., Huang Z.

Bone metastases is a common manifestation of advanced malignant tumors. With the recent advances in medical technology, the survival period of patients with malignant tumors is prolonged, and the probability of bone metastases is significantly increased. Approximately 70% to 80% of patients with breast or prostate cancer will eventually develop bone metastases. In addition, thyroid, lung, and kidney carcinomas are all known to cause bone metastases, with a 30% to 40% incidence upon postmortem assessment. Bone metastases often lead to severe pain, pathological fractures, and nerve damage and have become a critical factor affecting the quality of life and life expectancy of cancer patients. Although treatments for bone metastases are diverse, choosing the appropriate treatment is difficult. Both conservative treatment and open surgery have certain drawbacks and may not be appropriate for all patients. Interventional procedures have the advantages of less trauma with quicker recovery and represent a viable alternative. This review provides updates on the progress of research on the interventional treatment of bone metastases and directions regarding relevant further studies.

Ban J., Fock V., Aryee D.N., Kovar H.

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.

Bădilă A.E., Rădulescu D.M., Niculescu A., Grumezescu A.M., Rădulescu M., Rădulescu A.R.

In the last decades, the treatment of primary and secondary bone tumors has faced a slow-down in its development, being mainly based on chemotherapy, radiotherapy, and surgical interventions. However, these conventional therapeutic strategies present a series of disadvantages (e.g., multidrug resistance, tumor recurrence, severe side effects, formation of large bone defects), which limit their application and efficacy. In recent years, these procedures were combined with several adjuvant therapies, with different degrees of success. To overcome the drawbacks of current therapies and improve treatment outcomes, other strategies started being investigated, like carrier-mediated drug delivery, bone substitutes for repairing bone defects, and multifunctional scaffolds with bone tissue regeneration and antitumor properties. Thus, this paper aims to present the types of bone tumors and their current treatment approaches, further focusing on the recent advances in new therapeutic alternatives.

Vičić I., Belev B.

Guerrieri A.N., Montesi M., Sprio S., Laranga R., Mercatali L., Tampieri A., Donati D.M., Lucarelli E.

Bone is the third most frequent site of metastasis, with a particular incidence in breast and prostate cancer patients. For example, almost 70% of breast cancer patients develop several bone metastases in the late stage of the disease. Bone metastases are a challenge for clinicians and a burden for patients because they frequently cause pain and can lead to fractures. Unfortunately, current therapeutic options are in most cases only palliative and, although not curative, surgery remains the gold standard for bone metastasis treatment. Surgical intervention mostly provides the replacement of the affected bone with a bioimplant, which can be made by materials of different origins and designed through several techniques that have evolved throughout the years simultaneously with clinical needs. Several scientists and clinicians have worked to develop biomaterials with potentially successful biological and mechanical features, however, only a few of them have actually reached the scope. In this review, we extensively analyze currently available biomaterials-based strategies focusing on the newest and most innovative ideas while aiming to highlight what should be considered both a reliable choice for orthopedic surgeons and a future definitive and curative option for bone metastasis and cancer patients.

Kniha K., Heussen N., Weber E., Möhlhenrich S.C., Hölzle F., Modabber A.

Purpose: Very high or low temperatures will lead to bone damage. The objective of this review was to analyze threshold values for thermal bone necrosis. Methods: Histological animal studies evaluating thermal effects on bone necrosis were selected via electronic and hand searches in English and German language journals until 1 November 2019. The outcome measures were temperature-exposure intervals and laser settings effecting bone damage. Furthermore, investigated parameters were the bone-to-implant contact ratios (BIC) and infrabony pockets around dental implants after thermal treatment. For quality assessment of studies, the CAMARADES study quality checklist was applied. Results: A total of 455 animals in 25 animal studies were included for data extraction after screening of 45 titles from 957 selected titles of the MEDLINE (PubMed), The Cochrane Library, Embase and Web of Science search. The threshold values for bone necrosis ranged between 47 °C and 55 °C for 1 min. A threshold value for cryoinsult and laser treatment has not yet been defined. However, temperatures in the vicinity of 3.5 °C produce a histologically proven effect on the bone and in the surrounding tissue. At 50 °C for 1 min, BIC values significantly decreased and infrabony pockets increased. Bone quality had an influence on the outcome, as cancellous bone suffered higher bone damage from thermal treatment compared to cortical bone. Conclusion: No clear threshold value for bone necrosis is available according to the current literature for warm and cold stimuli. More in-depth and clinical studies are required to provide further insights in assessing the potential of thermal necrosis for implant removal.

Kitridis D., Saccomanno M.F., Maccauro G., Givissis P., Chalidis B.

Introduction Percutaneous cementoplasty (PC) has been widely used for the stabilization of impending fractures of the proximal femur due to metastatic lesions. Augmented percataneous cementoplasty (APC) with fixation devices aims to improve mechanical consolidation and stability of the construct. However, the clinical benefit of the combined technique has not been clearly established. The purpose of the current review was to compare the efficacy between APC and PC for impending pathologic proximal femoral fractures from metastatic malignancy, in terms of pain relief, operative time and fracture related complication rates. Material and methods Medline, Scopus, and the Cochrane central register of controlled trials were searched for clinical studies up to July 2019. Studies relevant to cementoplasty of the proximal femur were included. The primary outcome of the study was pain relief as assessed using the Visual Analogue Scale (VAS) change. Secondary outcomes included incidence of post-intervention fracture, operative time and complication rate. Results Twelve studies with a total of 343 patients were included. No difference was found for all outcomes. For pain relief, pooled results showed a mean difference in VAS score -4.6 ± 1.7 for PC, and -4.3 ± 2.5 for APC (p = 0.41). Post-intervention fractures of the proximal femur occurred in 7% of patients with PC and in 5% of patients with APC (p = 0.4), and the mean duration of interventions was 57.9 ± 8.4 and 56.5 ± 27.5 min, respectively (p = 0.58). Cement leakage into the hip joint or the soft tissues occurred in 5% of cases in PC group and in 8% of cases in APC group (p = 0.16). Six patients in the APC group (4%) experienced major systemic complications, which were treated successfully. Conclusions APC does not seem to improve pain relief, fracture incidence, and operative time when compared with PC. Both techniques appeared effective in terms of resolution of symptoms, prevention of pathologic fractures, and early facilitation of weight-bearing. PC showed more clinical safety, as no major systemic complications occurred. However, due to the relative paucity of large clinical trials, the decision of augmentation of cementoplasty should be individualized according to the size and location of metastatic lesions and the overall medical condition of patients.

Sas A., Van Camp D., Lauwers B., Sermon A., van Lenthe G.H.

Prophylactic treatment is advised for metastatic bone disease patients with a high risk for fracture. Femoroplasty provides a minimally invasive procedure to stabilize the femur by injecting bone cement into the lesion. However, uncertainty remains whether it provides sufficient mechanical strength to the weight-bearing femur. The goal of this study was to quantify the improvement in bone stiffness, failure load and energy to failure due to cement augmentation of metastatic lesions at varying locations in the proximal femur. Eight pairs of human cadaveric femurs were mechanically tested until failure in a single-leg stance configuration. In each pair, an identical defect was milled in the left and right femur using a programmable milling machine to simulate an osteolytic lesion. The location of the defects varied amongst the eight pairs. One femur of each pair was augmented with polymethylmethacrylate, while the contralateral femur was left untreated. Digital image correlation was applied to measure strains on the bone surface during mechanical testing. Only femurs with a critical lesion showed an improvement in failure load and energy to failure due to augmentation. In these femurs, bone strength improved with 28% (±17%) on average and energy to failure with 58% (±41%), while stiffness did not show a significant improvement. The strain measurements from digital image correlation showed that cement augmentation reinforced the lesion, resulting in reduced strain magnitudes in the bone tissue adjacent to the lesion. The results indicate that femoroplasty may be an effective treatment to prevent fractures in several metastatic bone disease patients. However, the large scatter in the data clarifies the need for developing strategies to identify those patients who will benefit the most from the procedure.

Turpin A., Duterque-Coquillaud M., Vieillard M.

Bone metastasis (BM) in cancer remains a critical issue because of its associated clinical and biological complications. Moreover, BM can alter the quality of life and survival rate of cancer patients. Growing evidence suggests that bones are a fertile ground for the development of metastasis through a "vicious circle" of bone resorption/formation and tumor growth. This review aims to outline the current major issues in the diagnosis and management of BM in the most common types of osteotropic cancers and describe the mechanisms and effects of BM. First, we discuss the incidence of BM through the following questions: Are we witnessing an increase in incidence, and are we now better equipped with modern imaging techniques? Is the advent of efficient bone resorption inhibitors affecting the bigger picture of BM management? Second, we discuss the potential effects of cancer progression and well-prescribed drugs, such as multitarget tyrosine kinase inhibitors, inhibitors of the mammalian target of rapamycin, and immune checkpoint inhibitors, on BM. Finally, we examine the duality of the effects of some therapies that may help in cancer treatment but may also contribute to further BM.