Karlijn Groenen

The effect of radiotherapy, and radiotherapy combined with bisphosphonates or RANK ligand inhibitors on bone quality in bone metastases. A systematic review

PURPOSE The role of radiotherapy in stabilizing metastatic bones is unclear. This systematic review assessed the effects of (1) radiotherapy, (2) radiotherapy combined with bisphosphonates, and (3) radiotherapy combined with RANK ligand (RANKL) inhibitors on bone quality and bone strength in bone metastases originating from solid tumors. METHODS Pubmed, EMBASE and the Cochrane Library were searched. Any type of study design and type and dose of radiotherapy, bisphosphonates and RANKL inhibitors were allowed. RESULTS 39 articles were identified. Animal studies showed that radiotherapy had similar effects on bone quality and strength as receiving no treatment, whereas adding bisphosphonates to radiotherapy restored bone quality and strength. In patient studies, bone density increased after radiotherapy and radiotherapy combined with bisphosphonates. However, due to the often non-optimal study design and study quality, it was unclear whether this increase could be attributed to these treatments. There was insufficient evidence to assess the additional effect of bisphosphonates or RANKL inhibitors. CONCLUSION Despite the clinical experience that radiotherapy is an effective treatment for bone metastases, there was no sufficient evidence for a positive effect on bone quality and fracture risk. Animal studies showed that adding bisphosphonates to radiotherapy restored bone quality and strength, whereas this was not proven in patients. There were no studies addressing the adjunct effect of RANKL inhibitors to radiotherapy. Although associated with several methodological, practical and ethical challenges, randomized controlled trials are needed.

Twente spine model: A complete and coherent dataset for musculo-skeletal modeling of the thoracic and cervical regions of the human spine.

Musculo-skeletal modeling could play a key role in advancing our understanding of the healthy and pathological spine, but the credibility of such models are strictly dependent on the accuracy of the anatomical data incorporated. In this study, we present a complete and coherent musculo-skeletal dataset for the thoracic and cervical regions of the human spine, obtained through detailed dissection of an embalmed male cadaver. We divided the muscles into a number of muscle-tendon elements, digitized their attachments at the bones, and measured morphological muscle parameters. In total, 225 muscle elements were measured over 39 muscles. For every muscle element, we provide the coordinates of its attachments, fiber length, tendon length, sarcomere length, optimal fiber length, pennation angle, mass, and physiological cross-sectional area together with the skeletal geometry of the cadaver. Results were consistent with similar anatomical studies. Furthermore, we report new data for several muscles such as rotatores, multifidus, levatores costarum, spinalis, semispinalis, subcostales, transversus thoracis, and intercostales muscles. This dataset complements our previous study where we presented a consistent dataset for the lumbar region of the spine (Bayoglu et al., 2017). Therefore, when used together, these datasets enable a complete and coherent dataset for the entire spine. The complete dataset will be used to develop a musculo-skeletal model for the entire human spine to study clinical and ergonomic applications.

Twente spine model: A complete and coherent dataset for musculo-skeletal modeling of the lumbar region of the human spine

Musculo-skeletal modeling can greatly help in understanding normal and pathological functioning of the spine. For such models to produce reliable muscle and joint force estimations, an adequate set of musculo-skeletal data is necessary. In this study, we present a complete and coherent dataset for the lumbar spine, based on medical images and dissection measurements from one embalmed human cadaver. We divided muscles into muscle-tendon elements, digitized their attachments at the bones and measured morphological parameters. In total, we measured 11 muscles from one body side, using 96 elements. For every muscle element, we measured three-dimensional coordinates of its attachments, fiber length, tendon length, sarcomere length, optimal fiber length, pennation angle, mass, and physiological cross-sectional area together with the geometry of the lumbar spine. Results were consistent with other anatomical studies and included new data for the serratus posterior inferior muscle. The dataset presented in this paper enables a complete and coherent musculo-skeletal model for the lumbar spine and will improve the current state-of-the art in predicting spinal loading.

Case-specific non-linear finite element models to predict failure behavior in two functional spinal units: FE TO PREDICT VERTEBRAL FAILURE

Current finite element (FE) models predicting failure behavior comprise single vertebrae, thereby neglecting the role of the posterior elements and intervertebral discs. Therefore, this study aimed to develop a more clinically relevant, case‐specific non‐linear FE model of two functional spinal units able to predict failure behavior in terms of (i) the vertebra predicted to fail; (ii) deformation of the specimens; (iii) stiffness; and (iv) load to failure. For this purpose, we also studied the effect of different bone density–mechanical properties relationships (material models) on the prediction of failure behavior. Twelve two functional spinal units (T6‐T8, T9‐T11, T12‐L2, and L3‐L5) with and without artificial metastases were destructively tested in axial compression. These experiments were simulated using CT‐based case‐specific non‐linear FE models. Bone mechanical properties were assigned using four commonly used material models. In 10 of the 11 specimens our FE model was able to correctly indicate which vertebrae failed during the experiments. However, predictions of the three‐dimensional deformations of the specimens were less promising. Whereas stiffness of the whole construct could be strongly predicted (R2 = 0.637–0.688, p < 0.01), we obtained weak correlations between FE predicted and experimentally determined load to failure, as defined by the total reaction force exhibiting a drop in force (R2 = 0.219–0.247, p > 0.05). Additionally, we found that the correlation between predicted and experimental fracture loads did not strongly depend on the material model implemented, but the stiffness predictions did. In conclusion, this work showed that, in its current state, our FE models may be used to identify the weakest vertebra, but that substantial improvements are required in order to quantify in vivo failure loads.

The Dutch national guideline on metastases and hematological malignancies localized within the spine; a multidisciplinary collaboration towards timely and proactive management

Here, we describe the development of a Dutch national guideline on metastases and hematological malignancies localized within the spine. The aim was to create a comprehensive guideline focusing on proactive management of these diseases, enabling healthcare professionals to weigh patient perspectives, life expectancy, and expected outcomes to make informed treatment recommendations. A national multidisciplinary panel consisting of clinicians, a nurse, a patient advocate, an epidemiologist, and a methodologist drafted the guideline. The important role of patients in the realization of the guideline enabled us to identify and address perceived shortcomings in patient care. The guideline covers not only metastatic epidural spinal cord compression, but also the treatment of uncomplicated metastases and hematological malignancies localized within the spine. The guideline is applicable in daily practice and provides an up-to-date and concise overview of the diagnostic and treatment possibilities for patients suffering from a disease that can have a serious impact on their quality of life. Suggestions for the practical implementation of patient care in hospitals are also provided, including approaches for pursuing proactive management. The crucial role of the patient in decision making is emphasized in this guideline.

Clinical Evaluation of the Spinal Instability Neoplastic Score in Patients Treated With Radiotherapy for Symptomatic Spinal Bone Metastases

Study Design. Retrospective cohort study. Objective. To determine the predictive value of the Spinal Instability Neoplastic Score (SINS) in a cohort of patients treated with radiotherapy for spinal bone metastases. Summary of Background Data. Assessment of spinal stability in metastatic disease is challenging and is mostly done by relying on clinical experience, in the absence of validated guidelines or an established predetermined set of risk factors. The SINS provides clinicians with a tool to assess tumor-related spinal instability. Methods. A total of 110 patients were included in this retrospective study. Time to event was calculated as the difference between start of radiotherapy and date of occurrence of an adverse event or last follow-up, with death being considered a competing event. A competing risk analysis was performed to estimate the effect of the SINS on the cumulative incidence of the occurrence of an adverse event. Results. Sixteen patients (15%) experienced an adverse event during follow-up. The cumulative incidence for the occurrence of an adverse event at 6 and 12 months was 11.8% (95% confidence interval 5.1%–24.0%) and 14.5% (95% confidence interval 6.9%–22.2%), respectively. Competing risk analysis showed that the final SINS classification was not significantly associated with the cumulative incidence of an adverse event within the studied population. Conclusion. The clinical applicability of the SINS as a tool to assess spinal instability seems limited. Level of Evidence: 3