What’s New in Musculoskeletal Tumor Surgery

The literature on musculoskeletal tumors continues to be robust; however, it has been dominated by retrospective observational studies. For bone sarcomas, cytotoxic chemotherapy remains the mainstay of systemic therapy, with no new, effective, targeted biologic interventions. There has been a renewed focus on functional outcomes and socioeconomic factors associated with oncologic outcomes and ongoing interest in pelvic reconstruction, which continues to have high rates of surgical complications. Limb reconstruction with biologic constructs, endoprosthetics, or a combination thereof continues to be successful in limb salvage, with higher revision rates in the pediatric population. With regard to skeletal metastases, there is growing interest in advanced radiation therapy protocols, machine learning algorithms for predicting patient survival, and expansion of the indications for resection and reconstruction rather than internal fixation for long-bone metastases, due to longer life expectancies in many patients with advanced carcinomas. With regard to soft-tissue sarcoma, several studies have highlighted the importance of early diagnosis and treatment. In addition, cytotoxic chemotherapy remains the mainstay of systemic treatment for advanced disease, with no notable breakthroughs in targeted biologic approaches or immunotherapy. However, an important potential paradigm shift in radiation therapy treatment has been suggested by studies on shorter courses of hypofractionated neoadjuvant radiation therapy, which may allow for the compression of the time frame between diagnosis and the surgical procedure. There has also been some interest in unique soft-tissue sarcoma subtypes and predictors of wound-healing complications. The most exciting advances have been in nonmalignant soft-tissue tumors. Studies have shown successful disease control with targeted biologic therapies for desmoid tumors and tenosynovial giant cell tumors. Finally, there has been a growing interest in intraoperative fluorescence to guide surgical margins in soft-tissue sarcoma. Bone Tumors Systemic Therapy Chemotherapy remains the cornerstone of systemic treatment for both Ewing sarcoma and osteosarcoma. In a notable randomized controlled trial, Brennan et al. evaluated chemotherapy regimens in patients with Ewing sarcoma1. Patients were randomized to receive the European regimen consisting of vincristine, ifosfamide, doxorubicin, and etoposide induction, and consolidation using vincristine, actinomycin D, and either ifosfamide alone, cyclophosphamide alone, or busulfan plus melphalan, or to receive the U.S. regimen of vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide induction, plus ifosfamide and etoposide, and consolidation using vincristine and either cyclophosphamide alone or actinomycin D plus ifosfamide, with busulfan and melphalan. The authors demonstrated that the U.S. regimen was more effective, less toxic, and shorter in duration and should be the international standard of care for patients with Ewing sarcoma moving forward. Oncologic and Functional Outcomes There is ongoing research focused on the predictors of oncologic outcomes in patients with sarcoma. Richardson et al. examined the relationships between tumor necrosis, survival, and social determinants of health in patients with osteosarcoma2. They found that a tumor necrosis threshold of 90% provided the best prognostic value and lower tumor necrosis levels were associated with worse survival. Lower socioeconomic status and uninsured status were negatively associated with a tumor necrosis level of ≥90%. Kim et al. investigated the clinical presentation of and detection methods for secondary osteosarcoma in patients who had survived retinoblastoma3. The results revealed that these secondary osteosarcomas had a predilection for the diaphysis of long bones and that regular surveillance, such as radionuclide bone scans, was effective in detecting secondary osteosarcomas. In a systematic review and meta-analysis, Gonzalez et al. demonstrated that patients with osteosarcoma presenting with pathologic fractures had lower 3-year and 5-year overall survival rates4. However, patients who presented with a pathologic fracture and underwent a limb-salvage surgical procedure had similar rates of local recurrence compared with patients who underwent amputation, suggesting that a pathologic fracture may not be an absolute contraindication to a limb-salvage surgical procedure. Several recent studies have explored functional outcomes in patient with primary bone tumors. Gazendam et al. aimed to define minimally important differences for both the Musculoskeletal Tumor Society score and the Toronto Extremity Salvage Score in patients undergoing a limb-salvage surgical procedure and endoprosthetic reconstruction for lower-extremity tumors5. These newly established minimally important differences provide valuable benchmarks for assessing the effectiveness of interventions in this population. Rizkallah et al. demonstrated comparable functional outcomes in patients who underwent proximal femoral replacement with preservation of the greater trochanter and those who underwent direct abductor muscle reattachment6. However, the group with greater trochanter preservation had lower dislocation rates. Gazendam et al. reviewed patients undergoing a limb-salvage surgical procedure and endoprosthetic reconstruction around the knee and evaluated the utility of intraoperative tourniquet use7. They demonstrated that the use of an intraoperative tourniquet was associated with better early functional outcome, as well as a shorter operative time and a reduced length of hospital stay. Ramsey et al. reported on the outcomes of patients who underwent a tibial turnup-plasty for chronic infection following oncologic reconstructions8. They established that this salvage procedure resulted in acceptable function and is a surgical option that can avoid a high transfemoral amputation or hip disarticulation. Finally, Geiger et al. examined the risk factors and outcomes of late amputation in pediatric patients with lower-extremity sarcomas9. They found that both primary and late amputation were associated with decreased physical health-related quality-of-life outcomes. There is an evolving understanding of how socioeconomic factors can impact outcomes in patients with sarcoma. Fujiwara et al. investigated the relationships between geographic access, institutional treatment volume, and survival in patients with bone sarcomas in the United States10. They found that high-volume facilities (≥20 cases per year) were associated with better survival outcomes. Yatham et al. focused on the association between insurance status and stage at diagnosis of patients with chondrosarcoma in the United States11. Uninsured patients had a significantly higher likelihood of being diagnosed at an advanced stage compared with insured patients. The study underscores the importance of health-care access and the need to address disparities in insurance coverage to improve early detection and outcomes for patients with chondrosarcoma. Pelvic Reconstruction The treatment and reconstruction of pelvic tumors continue to be active areas of interest in the literature. Rizkallah et al. reported on the medium-term outcomes of pelvic reconstruction utilizing the LUMiC endoprostheses (Implantcast) and demonstrated low rates of aseptic loosening, with dislocation and infection being the most common major complications12. Xie et al. evaluated the utility of a custom hemipelvic endoprosthesis with preservation of the femoral head in patients with primary bone malignancies and found acceptable function and oncologic outcomes at an early follow-up13. Hinckley et al. retrospectively reviewed patients who underwent pelvic reconstruction with a custom ilium monoflange prosthesis14. They found 92% survivorship at a minimum follow-up of 2 years and concluded that the prosthesis provided durable short-term fixation. Zhang et al. performed a multicenter review of patients who underwent hip transposition after internal hemipelvectomy for periacetabular bone sarcomas15. They demonstrated that most patients were able to regain ambulatory function by 2 months postoperatively and concluded that hip transposition is a viable alternative to endoprosthetic reconstruction in this population. Finally, Dunbar et al. evaluated the impact of psoas muscle size in patients who underwent internal hemipelvectomy without reconstruction16. They established that rehabilitation resulting in increased postoperative psoas size was correlated with improvements in functional outcomes. Pelvic tumor surgical procedures are fraught with complications, and recent literature has provided insight into potential risk factors. Gonzalez et al. focused on the 30-day soft-tissue complications following the resection of bone and soft-tissue sarcomas of the pelvis17. Older age, hematocrit of <30%, and longer operative time were identified as risk factors for postoperative soft-tissue complications. Bensaid et al. analyzed the risk of surgical site infection in patients undergoing pelvic bone and soft-tissue resection18. They revealed a 41% rate of postoperative surgical site infection and found that extended antibiotic prophylaxis postoperatively did not reduce infection rates. Qu et al. evaluated the position of the acetabular component following periacetabular tumor resection and endoprosthetic reconstruction19. They demonstrated that the hip center of rotation was significantly shifted anteriorly and inferiorly in most patients who sustained a dislocation compared with the patients who did not sustain a dislocation. Biologic Reconstruction Biologic reconstruction following the resection of primary bone tumors continues to be a widely utilized technique and an area of active interest. Jamshidi et al. compared osteoarticular allograft alone with allograft-prosthesis composite (APC) reconstruction for skeletally immature patients with distal femoral tumors20. The authors demonstrated that APC reconstructions provided better stability and lower rates of radiographic osteoarthritic changes, whereas the group with allograft alone demonstrated better knee range of motion at the 7-year follow-up. Gundavda et al. provided a detailed description of the Toronto Sarcoma Protocol for reconstructive allograft preparation for long-bone intercalary segment reconstruction21. Jamishidi et al. reported on the utility of fibular strut allografts for skeletally mature patients with pathologic fractures secondary to proximal humeral unicameral bone cysts22. Patients typically had osseous union within 3 months and excellent postoperative functional outcome scores. Syvänen et al. conducted a randomized controlled trial comparing the use of allograft with that of bioactive glass (BG-S53P4; Bonalive) following intralesional curettage of benign bone cysts in 51 pediatric patients23. The authors found comparable recurrence and complication rates between the 2 groups. Endoprosthetic Outcomes Endoprosthetic reconstructions remain the mainstay for reconstruction following resection of periarticular bone tumors. El Ghoneimy et al. performed a single-center retrospective review evaluating the survivorship and complications of pediatric patients with cementless distal femoral endoprostheses24. The authors reported an 8-year cumulative incidence of revision surgical procedures of 32%, with hinge breakage being the most common indication for revision, and evidence of radiographic stress shielding in 26% of patients. Geiger et al. reported on the survivorship of both primary and revision cemented distal femoral endoprostheses25. They found that the revision group demonstrated shorter mean implant survival time, with all-cause revision as the end point, and found that a stem diameter of <15 mm was an independent risk factor for all-cause revision. Arnold et al. evaluated the impact of radiation on implant survivorship in patients undergoing lower-extremity endoprosthetic reconstruction26. The authors demonstrated lower mean implant survival time in patients who underwent high-dose radiation compared with patients who underwent no radiation. Tanaka et al. performed a multi-institutional review of pediatric patients with distal femoral bone malignancies who underwent reconstruction with the Compress Compliant Pre-Stress spindle (Zimmer Biomet) paired with an Orthopedic Salvage System expandable distal femoral endoprostheses (Zimmer Biomet)27. The authors found high rates of osseointegration of the Compress spindle but high rates of failure of the expandable endoprosthetic device. Spinal Bone Tumors Spinal bone tumors remain a challenging clinical entity. Kolz et al. reviewed a series of patients undergoing treatment for chordomas in the mobile spine and found a poor overall survival of 39% at 5 years28. However, the authors found that surgical resection was beneficial in preventing new neurologic deficits. Similarly, through the California Cancer Registry, Stroud et al. evaluated patients with primary bone malignancies of the mobile spine29. Patients who underwent standard treatment had lower mortality rates when compared with patients who did not undergo any known treatment. Patients who underwent treatment at a National Cancer Institute-designated Cancer Center (NCICC) were more likely to undergo standard treatment protocols. Giant Cell Tumor Several recent studies have provided valuable insights into giant cell tumors30–32. In a systematic review, Trovarelli et al. highlighted that multicentric giant cell tumors primarily affect young individuals and often present as metachronous tumors30. Local recurrence and distant metastases were common; multicentric tumors tend to occur in younger people with a metachronous pattern, and this subset of patients with giant cell tumors should be followed closely. Aoude et al. investigated risk factors for tumor relapse in patients with giant cell tumors who underwent joint-salvage procedures31. The authors found that curettage was associated with a higher risk of local recurrence compared with resection. Younger age and tumors in the distal radius were identified as factors contributing to higher rates of recurrence. A repeated joint-salvage surgical procedure was successful in treating the majority of patients with local relapse. Moore et al. evaluated the cytotoxic effects of commonly used irrigation solutions on chondrosarcoma and giant cell tumor cells32. They found that a 0.05% chlorhexidine gluconate solution showed high cytotoxicity, suggesting its potential as a chemical adjuvant during intralesional curettage of both chondrosarcoma and giant cell tumors. Skeletal Metastases Radiation Therapy Management There is ongoing interest in the use of novel radiotherapies for the treatment of skeletal metastases. Mascia et al. investigated the feasibility of proton FLASH radiation therapy for symptomatic bone metastases33. The proton FLASH protocol was clinically feasible, had minimal adverse events, and was found to provide pain relief similar to conventional-dose-rate photon radiation therapy. Ryu et al. completed a Phase-3 randomized controlled trial comparing the efficacy of stereotactic radiosurgery with that of conventional radiation therapy for localized vertebral metastases34. The authors demonstrated no superiority of stereotactic radiosurgery compared with conventional radiation therapy with regard to patient-reported pain at the 3-month follow-up. Surgical Management The surgical management of skeletal metastases is evolving, and several studies have evaluated various surgical techniques and outcomes in this patient population. Kendal et al. assessed the indications for and survivorship of endoprosthetic reconstruction in patients with extremity metastatic disease35. Endoprosthetic reconstructions were most commonly performed for patients with renal cell carcinoma and demonstrated a low implant failure rate. Johnson et al. evaluated the survivorship of intercalary endoprosthetic reconstruction for diaphyseal bone metastases of the humerus and femur36. They demonstrated a cumulative incidence of implant revision of 11% at 1 year and 16% at 5 years, suggesting adequate survivorship in this patient population. Cevolani et al. evaluated the efficacy of the addition of electrochemotherapy to intramedullary nailing in patients undergoing a surgical procedure for metastatic bone disease37. The authors showed that pain levels decreased significantly, and the risk of local disease progression was low. De Groot et al. reevaluated the Skeletal Oncology Research Group (SORG) machine learning algorithm to predict survival in patients with metastatic bone disease undergoing surgical intervention38. The authors demonstrated that the SORG machine learning algorithm underestimated survival in a contemporary group of patients undergoing innovative immunotherapy and highlighted the importance of periodic reassessment of probability calculators as treatment regimens evolve. Soft-Tissue Sarcoma Epidemiology and Outcomes Prediction Several studies assessed epidemiology and predictive factors for outcomes in soft-tissue sarcoma. Brennan and Singer’s historical analysis of sarcoma care at Memorial Sloan Kettering Cancer Center revealed substantial advancements in surgical techniques over 5 and patient outcomes with surgical procedures and the of sarcoma surgical In a retrospective et al. examined the of and risk factors for soft-tissue sarcomas in in the United The revealed that had an increased risk of soft-tissue sarcoma following radiation therapy, with an overall incidence rate of per and younger age at higher radiation and longer time radiation therapy as risk factors. study the importance of and follow-up for who have radiation therapy. Gonzalez et al. examined the prognostic and predictive factors in sarcoma using a care center and found that tumor tumor and the of were prognostic factors associated with overall survival and survival in patients with Ryu et al. investigated the effects of time to treatment on outcomes for patients with soft-tissue sarcomas and found that longer time between diagnosis and the surgical procedure or between diagnosis and radiation therapy were to et al. examined the impact of insurance status on mortality rates in with sarcoma of the and The revealed that uninsured and patients had higher mortality rates compared with insured patients. Finally, et al. a prognostic score for patients with sarcoma and metachronous metastases who underwent and found that primary tumor the of metastases, and the of metastases were associated with worse overall Systemic Therapy There have been some notable studies evaluating systemic treatment for soft-tissue sarcoma. et al. a study focused on and young with using European Sarcoma Group The authors found that these resulted in outcomes in of survival and overall survival rates in this age international study by et al. was a analysis of chemotherapy regimens for advanced sarcoma in The authors found that regimens were the most and provide clinical being in et al. compared the efficacy of alone with the combination of and followed by alone as the therapy for metastatic or and demonstrated that the combination therapy followed by alone significantly survival compared with However, there was no in overall survival between the 2 treatment groups. In a study by et in patients with metastatic or advanced had an rate of and disease control rate of The survival was and the overall survival was With regard to new biologic therapies and et al. evaluated the use of neoadjuvant in soft-tissue sarcomas and reported a higher risk of major complications associated with this treatment Finally, in a trial, et al. investigated the efficacy and of the and in patients with advanced or metastatic soft-tissue and bone demonstrated with Radiation Therapy With regard to advances in radiation therapy, et al. conducted a trial evaluating a radiation therapy regimen for patients with soft-tissue The study demonstrated that this treatment was feasible, with acceptable levels and rates of pathologic The authors also reported local control and overall survival the potential effectiveness of this treatment et al. reviewed with an intraoperative radiation therapy in extremity sarcoma treatment and demonstrated local control rates and overall survival with low rates of Finally, et al. evaluated the clinical outcomes of patients with localized soft-tissue sarcoma with neoadjuvant or radiation The showed that a to a pathologic was associated with overall survival and survival. the study demonstrated that the addition of chemotherapy to radiation therapy did not significantly improve outcomes compared with radiation therapy Soft-Tissue Sarcoma Several studies assessed treatment and outcomes in unique soft-tissue sarcoma et al. found that patients with localized sarcomas had better survival outcomes compared with those with metastatic disease and identified tumor and surgical status as prognostic factors associated with patient et al. investigated the and outcomes of patients with chondrosarcoma using the United Sarcoma The authors found that most patients with chondrosarcoma had localized disease at diagnosis and that these patients had a 5-year overall survival rate of et al. assessed the impact of radiation therapy on survival in patients with and found that the of to radiation therapy was associated with et al. evaluated the treatment outcomes of patients with Ewing sarcoma and reported that patients who underwent therapy, a surgical and had overall survival and survival compared with those who underwent a surgical procedure The authors also reported that tumor size and the of at diagnosis were factors associated with worse outcomes. Finally, et al. reported that local with margins is an effective treatment for to low rates of recurrence and The study also explored the use of and found it to be an treatment option for cases of to the surgical treatment of soft-tissue sarcoma continue to be an important area of et al. analyzed the National Surgical to risk factors associated with 30-day complications following lower-extremity sarcoma and found that age, higher Society of radiation therapy, longer operative time, and procedures were associated with an increased likelihood of postoperative Ramsey et al. investigated the addition of coverage to antibiotic prophylaxis during soft-tissue sarcoma resection is associated with a in the rate of complications and found that the addition of coverage did not significantly reduce the of complications compared with standard antibiotic In a et al. aimed to the of using in patients with musculoskeletal tumors and reported that a of patients demonstrated of suggesting an increased risk of et al. investigated the of as a of wound-healing complications in patients with soft-tissue sarcoma, and found that were not significantly associated with wound-healing These results the need for alternative methods or risk to predict and wound-healing complications in patients who had of a soft-tissue sarcoma. Finally, et al. analyzed the outcomes of surgical reconstruction in patients with extremity and soft-tissue sarcoma, using the U.S. Sarcoma and provided valuable on the effectiveness of and complications associated with surgical techniques in sarcoma to Soft-Tissue Tumors Tumors There have been some advancements in the treatment of desmoid tumors. et al. investigated the use of a for the treatment of desmoid tumors and reported that treatment resulted in a substantial rate and survival in patients with desmoid In addition, et al. demonstrated that the addition of the of to clinical factors the of local recurrence in patients with desmoid Giant Cell Tumor The treatment of tenosynovial giant cell tumors continues to be an area of ongoing et al. reported the efficacy of with regard to pain relief for patients within the study and found that treatment resulted in pain In a et al. examined the surgical management of patients with tenosynovial giant cell tumors in a and highlighted the importance of surgical approaches in successful outcomes for patients with tenosynovial giant cell authors have focused on intraoperative to resection. et al. demonstrated that fluorescence the and of surgical in the of tumor et al. assessed the use of fluorescence to disease during the surgical procedure for bone and soft-tissue tumors and demonstrated the potential of this technique in tumor for more tumor The in Tumor The trial was in and the was to to secondary A of secondary were in a These important studies address several the risk factors for surgical site infection and following lower-extremity endoprosthetic reconstruction, functional outcomes in pediatric patients compared with the use of in the the use of therapy and postoperative and the risk for surgical site the risk of following lower-extremity endoprosthetic reconstruction, and and on surgical and outcomes. of the studies in the be provided in the Musculoskeletal Tumor

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