Emerging innovations and advancements in the field of musculoskeletal oncology.

Orthopaedic oncology has evolved dramatically as a discipline over the past 50 years.1-4 With the advent of subspecialty fellowship training and transdisciplinary collaboration, our field has pushed the intellectual boundaries on several academic fronts, some of which we will highlight in this special edition of JSO. Broadly, we have chosen to focus on (1) outcomes, disparities and quality of life; (2) surgical management and technological developments; and (3) nonsurgical advancements. These areas are helping to redefine the standard of care. We hope the reader will enjoy this update on these salient, dynamic aspects of orthopaedic oncology. As recent trends in healthcare have focused on value-based initiatives, all providers are challenged with delivering expert care while also optimizing patient-perceived outcomes.5 Patient reported outcome measures (PROMs) have shifted the clinical focus from the objective assessment of providers to the subjective perspective of the patient.4, 5 With the creation of specific population databases and institutional collaborations, we are now able to research the subjective impact of our treatment and management of patients with musculoskeletal tumors.5-11 Cizik, Blank and associates provide a description of the pertinent advances in this specific research area as it relates to orthopaedic oncology patients. The importance of PROMs to orthopedic oncology care is complemented by the recent increased focus on socioeconomic considerations in the management of these complex patients. Socioeconomic determinants of health (SDOH) may influence outcomes in ways not previously appreciated.12-17 It has been demonstrated in several studies that insurance status alone, for example, can predict stage at presentation, type of surgical management and survivorship in patients presenting with a musculoskeletal oncologic condition.12, 14 The need to improve access and limit discrepancies in care and outcomes in disadvantaged populations is critical in advancing our ability to care for the overall health of the greater population. The influence of SDOH for patients seeking highly specialized orthopaedic oncology care cannot be underestimated and will be reviewed by Jawad et al.12 To round out these social considerations, Goulding et al., will highlight the literature regarding the evaluation of quality of life in sarcoma patients. This will include a review of the impact of both surgical and nonsurgical interventions in the management of these rare disease entities.18, 19 Skeletally related events make up approximately 20% of the US cancer care economy.20 We owe it to our patients afflicted with metastatic bone disease (MBD) to be the primary stewards of their musculoskeletal health.21 Breast, prostate, and lung cancer are the three most prevalent types of cancer diagnosed in the United States, all of which have a propensity to metastasize to bone.22 Bone metastases are known to have significant medical and quality of life implications through the risk of impending and realized fractures, hypercalcemia, possible spinal cord compression and spinal disease.23-26 Kafchinski et al., will review the current concepts and practices in caring for patients with MBD. Advances in the understanding of the differences in the management of disease specific metastatic conditions will also be analyzed, including the evolving concept of metastatectomy. For example, the impact of metastatectomy on overall survival of patients with metastatic renal cell carcinoma has been a topic of debate and controversy for years.27, 28 With improving medical management and increasing survival of metastatic cancer patients, maintaining durable functional outcomes for these patients grows even more critical to their overall outcome and quality of life. In particular, metastatic disease to the pelvis and acetabulum represents an area of significant surgical complexity. Historically, extensive surgical interventions have been necessary to temporize pain and optimize function. Accordingly, surgery was frequently deferred because of the morbidity of such procedures in relatively sick patients with a short life expectancy.29, 30 As patients are living longer with the burden of MBD, surgeons have been pressed to develop less invasive techniques afforded by advancing technology. This has been particularly relevant in pelvis and periacetabular disease31, 32 and will be reviewed by Lerman et al. In addition to the surgical management of metastatic disease of the pelvis, technological advances have been made in how we care for primary pelvic bone sarcomas. Such resections and reconstructions comprise some of the most surgically complex procedures we perform as orthopaedic oncologists. Understanding that resections without a reconstruction can result in impaired function,33, 34 there has been a demand to develop more efficient and precise reconstructive options. Throughout the field of orthopaedic surgery, the production of 3D custom implants has become increasingly popular. Nystrom et al., will provide insights into how these complex pelvis reconstructions have proven highly advantageous, affording surgeons the ability to reconstruct irregularly shaped defects with preplanned fixation strategies, hopefully with the result of improving functional outcomes of these patients postoperatively.34-36 An exciting emerging reconstruction option is the push to advance technological function solutions for patients with complex amputations. In certain situations where amputation cannot be avoided as the optimal treatment for our patients, it can be difficult to achieve one of our field's primary goals of maximizing function with the use of external prosthetics. More specifically, the role of osseo-integrative devices in amputees has some favorable early results.37, 38 Forsberg et al., will discuss the promising emerging developments in the field of osseo-integrative applications in the setting of amputation. Reaching beyond the diagnostic and technical domains of musculoskeletal oncology care, understanding the dynamic interplay between cancer cells and the bone microenvironment will increasingly influence preventative and therapeutic strategies to optimize bone health in our cancer patients. Targeting cancer-mediated dysregulation of osteoclastic bone resorption using bisphosphonates and denosumab is now standard of care to reduce skeletal related events in advanced cancer patients.39, 40 Reviewed by Bhale and colleagues, additional insights into the how cancer cells dysregulate the bone microenvironment and how the bone response to cancer invasion fuels cancer progression will assist the discovery of novel local and systemic treatment strategies for patients with mono- and polyostotic bone disease. Last, the orthopedic oncologist often manages many benign yet locally aggressive and destructive diseases affecting the musculoskeletal system. One such entity is tenosynovial giant cell tumor, also known as pigmented villonodular synovitis or giant cell tumor of tendon sheath. This disease can be quite locally extensive with secondary bony destruction of the joint. For the diffuse type, local recurrence rates can be quite high despite aggressive surgical resection. Surgical management can be quite morbid with multiple attempts resulting in a very negative impact on function.41 In light of this, there has been a push for the development of nonsurgical treatments for this disease entity. The application of the selective CSF1R inhibitor, pexidartinib, in particular, has been promising in both an isolated treatment strategy and in conjunction with surgical management of advanced disease. Unfortunately, such agents as pexidartinib have been associated with some negative systemic side effects. Further improvements in treatment are needed.42, 43 One such promising application is the proposed intra-articular application of such medications, with research into this treatment strategy currently underway. Van de Sande et al., will provide an update on the latest developments The field of orthopaedic oncology is moving forward at an exciting pace as we strive to improve the care of patients afflicted with musculoskeletal neoplastic disease. This special edition is but a glimpse of select salient topics we hope the reader will find relevant to their practice. We are excited to offer these papers in hopes of stimulating your curiosity to further explore these and other advances in our wonderful discipline. Any data that support the findings within this manuscript are available from the corresponding author upon reasonable request. In this special seminar series, we highlight important surgical and nonsurgical advancements in the delivery of musculoskeletal oncology care. We also cover important aspects of care delivery disparities, patient reported outcomes, and measuring quality of life in this diverse and multifaceted patient population. These engaging and thought provoking topics provide a glimpse of the fast paced multidisciplinary progress within our exciting discipline