Pediatric Ewing Sarcoma Presentation, Treatment, and Outcomes Across Sociodemographic Groups.

INTRODUCTION: In this study, we evaluate the association between sociodemographics and disease presentation, treatment, and survival for children, adolescents, and young adults with Ewing sarcoma. METHODS: Case-level data were downloaded from The Surveillance, Epidemiology, and End Results database. Cases included patients ages 0-24 who were diagnosed with Ewing sarcoma between 2004 and 2020. RESULTS: One thousand two hundred forty four patients were included in the analysis. When compared to non-Hispanic White (NHW) patients, Hispanic patients were more likely to present with tumors ≥8 cm (odds ratio (OR) = 1.71, 95% confidence interval (CI) = 1.24-2.36) and metastases (OR = 1.65, 95% CI = 1.23-2.20). Black patients were less likely to receive chemotherapy (OR = 0.25, 95% CI = 0.07-0.97). The 5-year disease-specific survival rate was 73% for NHW patients, 65% for Black patients, 67% for Asian patients and 66% for Hispanic patients. When accounting for confounding factors, Hispanic and Asian patients had higher probabilities of death due to cancer compared to NHW patients (HR = 1.41, 95% CI = 1.10-1.81; HR = 1.64, 95% CI = 1.09-2.48, respectively). Young adults and adolescents were significantly more likely to present with metastases, experience ≥1 month between diagnosis and treatment, and had lower survival. CONCLUSIONS: Significant differences in Ewing sarcoma presentation, treatment, and survival were observed across age groups and race/ethnicity. Future work should focus on expanding access to care in underserved groups. Further qualitative studies could assist in determining the exact factors that prevent patients from accessing care or examine how genetic factors that contribute to Ewing sarcoma severity differ across demographic groups.

Does a Concise Patient-reported Outcome Measure Provide a Valid Measure of Physical Function for Cancer Patients After Lower Extremity Surgery?

BACKGROUND: Current functional assessment tools for orthopaedic oncology are long surveys that contribute to patients' survey fatigue and yet lack the ability to discern meaningful differences in a patient population that is often mobile but unable to perform strenuous activities. We sought to determine whether a shorter, novel tool based on existing, validated surveys could better capture differences in a sample of orthopaedic oncology patients. QUESTIONS/PURPOSES: (1) Can a concise fixed-item functional tool derived from the 50 items in the Toronto Extremity Salvage Score for the lower extremity (TESS LE) and the Lower Extremity Functional Scale (LEFS) demonstrate similar responsiveness in terms of sensitivity and specificity? (2) What is the precision and accuracy of the concise tool compared with the TESS LE and LEFS? METHODS: Functional outcome data were collected and maintained in a longitudinally maintained database at a single institution. Patients were included in the study if (1) they had undergone a tumor excision or a nononcologic orthopaedic procedure (for example, arthroplasty for osteoarthritis) for a bone or soft tissue tumor affecting lower extremity function, and (2) they had completed the LEFS, TESS LE, and Patient-Reported Outcomes Measurement Information System (PROMIS) global health tool on at least two clinic visits. Between September 2014 and April 2022, we treated 14,234 patients for primary bone or soft tissue sarcoma, metastatic disease to bone, or orthopaedic sequelae of chronic cancer care. Approximately 6% (854 of 14,234) were excluded due to the need of a language translator. Approximately 2% (278 of 13,380) refused or were unable to participate. Seventy-two percent (9433 of 13,102) of the patients had an operation on a lower extremity. Of these, 4% (339 of 9433) of the patients completed the TESS LE, LEFS, and Item 3 of the PROMIS global health tool on ≥ 2 clinic visits. Of the patients in the current study, 49% (167 of 339) were women, and 27% (93 of 339) had metastatic carcinoma. Twelve percent (41 of 339) of the patients died before the end of the study period. Spearman rank-order correlation, principal component analysis (PCA), and item response theory (IRT) modeling identified 14 highly discriminating items from the TESS LE and LEFS. Multiple linear stepwise regression (MLSR) was performed with the dependent variable being the summary score of the 14 items derived from the TESS LE and LEFS and standardized to a percentage of 100. The beta coefficient from the MLSR was used to derive a weight for each of the 14 items. Evaluation of the model with 10 to 17 variables was performed to ensure that the model with the 14 items met the most criteria for fit with the PCA, the receiver operating characteristic (ROC) curve, and the IRT modeling criteria. The responsiveness (sensitivity and specificity) of the change scores in the shortened 14-item survey, the 30-item TESS LE, and the 20-item LEFS as compared with the dichotomized changes in Item 3 of the PROMIS global health tool was evaluated using ROCs. The concordance (accuracy and precision) of the 14 items derived from the LEFS and TESS LE was evaluated. RESULTS: The responsiveness (sensitivity and specificity) of the shortened 14-item survey, the TESS LE, and the LEFS to the criterion target of the PROMIS global health tool (Item 3) was similar, with areas under the curve (AUCs) ranging from 0.62 to 0.65 for the ROC curves. The responsiveness of the 14-item survey to the TESS LE showed sensitivity of 96% and specificity of 90%, with an AUC of 0.98 (p < 0.001). The responsiveness of the 14 items to the LEFS showed sensitivity of 95% and specificity of 86%, with an AUC of 0.96. The validity of the 14 items to the TESS LE was measured by concordance, with a precision of 0.98 and an accuracy of 0.97. Concordance of the 14 items to the LEFS showed a precision of 0.98 and accuracy of 0.83. CONCLUSION: The concise 14 items derived from patient-reported responses in the TESS LE and LEFS outcome measures showed similar responsiveness (sensitivity and specificity) as the original TESS LE and LEFS for cancer patients after lower extremity orthopaedic surgery performed for oncologic and nononcologic indications. The concise 14 items have a similar ability to the TESS LE and LEFS to tell the clinician or patient how they are functioning compared with other patients. These 14 items are shorter than the combined 50 items of the TESS LE and LEFS while retaining the capacity to describe a broad range of lower extremity function for orthopaedic oncology patients. We have named the 14-item survey the Lower Extremity Oncology Functional Assessment Tool.Level of Evidence Level II, diagnostic study.

Moderately hypofractionated, preoperative radiotherapy in patients with soft tissue sarcomas (HYPORT-STS): Updated local control, late toxicities, and patient-reported outcomes.

BACKGROUND: Moderately hypofractionated, preoperative radiotherapy in patients with soft tissue sarcomas (HYPORT-STS; ClinicalTrials.gov identifier NCT03819985) investigated a radiobiologically equivalent, moderately hypofractionated course of preoperative radiotherapy (RT) 15 × 2.85 Gy in patients with soft tissue sarcoma (STS). Here, the authors report longer term follow-up to update local control and report late toxicities, as well as functional and patient-reported outcomes. METHODS: HYPORT-STS was a single-center, open-label, single-arm, prospective phase 2 clinical trial that enrolled 120 eligible adult patients with localized STS of the extremities or superficial trunk between 2018 and 2021. Patients received a 3-week course of preoperative RT followed by surgery 4-8 weeks later. End points and follow-up were analyzed from the date of surgery. RESULTS: The median follow-up was 43 months (interquartile range, 37-52 months), and the 4-year local recurrence-free survival rate was 93%. Overall RT-related late toxicities improved with time from local therapy (p < .001), and few patients had grade ≥2 toxicities (9%; n = 8 of 88) at 2 years. These included: 2% grade ≥2 skin toxicity, 2% fibrosis, 3% lymphedema, and 1% joint stiffness. Four patients (3%) had bone fractures. Both functional outcomes, as measured by the Musculoskeletal Tumor Society Rating Scale (p < .001), and quality of life, as measured by the Functional Assessment of Cancer Therapy-General (p < .001), improved with time from treatment, and both measures were better in follow-up at 2 years compared with baseline. CONCLUSIONS: Long-term follow up suggests that moderately hypofractionated preoperative RT for patients with STS is safe and effective. Higher grade late toxicities affect a minority of patients. Late toxicities decrease over time, whereas functional outcomes and health-related quality of life seem to improve with more time from combined modality treatment.

Utility of 3D-Printed Models in the Surgical Planning for Primary Spine Tumors: A Survey of International Spinal Oncology Experts.

STUDY DESIGN: Survey study. OBJECTIVES: The purpose of this study was to characterize the utility of 3D printed patient specific anatomic models for the planning of complex primary spine tumor surgeries. METHODS: A survey of individual members of an international study group of spinal oncology surgeons was performed. Participants were provided a clinical vignette, pathologic diagnosis, and pre-operative imaging for three primary spinal oncology cases. Study participants provided a free text surgical plan for resection and were then presented an associated 3D printed model for each case and asked to re-evaluate their surgical plan. RESULTS: Ten spinal oncology surgeons participated in the study, representing nine institutions across five countries. Four of the surgeons (40%) made significant changes to their surgical plan after reviewing the 3D models, including sacrifice of an additional nerve root to obtain negative margins, sparing an SI joint that was originally planned for inclusion in the en bloc resection, adjusting the location of osteotomy cuts, changes to the number of surgical stages and/or staging order, and preservation of neurology that was originally planned for sacrifice. The overall impression of the 3D models was positive, with 90% of the participants stating they found the 3D model useful in developing a surgical plan. CONCLUSIONS: Surgical planning for resection of primary spinal column tumors is challenging and time intensive. 3D printed patient specific surgical models may be an additional tool that can augment surgical planning and execution by improving the chance of accomplishing surgical resection goals and minimizing morbidity.

Computer-Aided Design and Manufacturing to Facilitate Microvascular Free Tissue Transfer in Extremity, Pelvic, and Spinal Reconstructions.

BACKGROUND: Numerous surgical fields have embraced computer-aided design and computer-aided manufacturing (CAD/CAM), including plastic and reconstructive surgery. However, most of the literature and clinical use pertains to reconstruction of the head and neck. Herein, we provide a case series and systematic review of the literature, documenting the use of CAD/CAM in facilitating complex microvascular free tissue transfer for reconstructions involving the extremities, pelvis, and spine (EPS). METHODS: This study consisted of two components: a case series and a systematic review of the literature. For the case series, the senior author's cases that included CAD/CAM to assist microvascular free tissue transfer reconstructions of the EPS were included. For the systematic review, all PubMed-, Scopus-, and Google Scholar-indexed studies describing the use of CAD/CAM to facilitate free tissue transfer in the EPS were identified and included using PRSMA guidelines. RESULTS: The case series identified 10 patients who received CAD/CAM-assisted microvascular reconstruction. Our systematic review identified 15 articles, representing 124 patients and 133 CAD/CAM-assisted free tissue transfers. Most authors believed that CAD/CAM facilitated a more efficient operation by shifting much of the intraoperative planning to the preoperative phase, ultimately translating to a shorter and more accurate surgery with improved function and cosmesis. CONCLUSION: CAD/CAM can be used to facilitate microvascular reconstruction of the EPS. Our cases series and systematic review suggest that CAD/CAM for EPS surgery may improve outcomes.

Can Periprosthetic Joint Infection of Tumor Prostheses Be Controlled With Debridement, Antibiotics, and Implant Retention?

BACKGROUND: Two-stage revision for periprosthetic joint infection (PJI) in patients who have undergone segmental replacement of the distal femur or proximal tibia after tumor resection can be associated with considerable morbidity, pain, and risk of complications because the procedure often results in removal of long, well-fixed stems from the diaphysis. A less-aggressive surgical approach, such as debridement, antibiotics, and implant retention (DAIR), may be attractive to patients and surgeons because of less morbidity, but the likelihood of eradicating infection in comparison to the traditional two-stage revision is not well established for oncology patients. Furthermore, the relative risk of subsequent amputation for DAIR versus two-stage revision has not been defined for this population. QUESTIONS/PURPOSES: (1) How does DAIR compare with two-stage revision in terms of infection control for patients with distal femoral or proximal tibial segmental modular endoprostheses? (2) Is DAIR as an initial procedure associated with an increased risk of amputation compared with two-stage revision for infection? METHODS: From the longitudinally maintained orthopaedic oncology surgical database at our institution, we identified 69 patients who had been treated for a clinical diagnosis of PJI at the knee between 1993 and 2015. We excluded 32% (22) of patients who did not meet at least one of the major criteria of the Musculoskeletal Infection Society (MSIS) for PJI, 3% (2) of patients who underwent immediate amputation, 3% (2) of patients who had a follow-up time of < 24 months, and 7% (5) of patients who did not have a primary tumor of the distal femur or proximal tibia. The study consisted of 38 patients, of whom eight underwent two-stage revision, 26 underwent DAIR, and four underwent extended DAIR (removal of all segmental components but with retention of stems and components fixed in bone) for their initial surgical procedure. To be considered free of infection, patients had to meet MSIS standards, including no positive cultures, drainage, or surgical debridement for a minimum of 2 years from the last operation. Factors associated with time-dependent risk of infection relapse, clearance, amputation, and patient survival were analyzed using Kaplan-Meier survivorship curves and the log-rank test to compare factors. Association of demographic and treatment factors was assessed using chi-square and Fisher exact tests. RESULTS: Continuous infection-free survival at 5 years was 16% (95% CI 2% to 29%) for patients undergoing DAIR compared with 75% (95% CI 45% to 100%) for patients undergoing two-stage revision (p = 0.006). The median (range) number of total surgical procedures was 3 per patient (1 to 10) for DAIR and 2 (2 to 5) for two-stage revision. Twenty-nine percent (11 of 38) of patients eventually underwent amputation. Survival without amputation was 69% (95% CI 51% to 86%) for DAIR compared with 88% (95% CI 65% to 100%) for two-stage revision at 5 years (p = 0.34). The cumulative proportion of patients achieving infection-free status (> 2 years continuously after last treatment) and limb preservation was 58% (95% CI 36% to 80%) for patients initially treated with DAIR versus 87% (95% CI 65% to 100%) for patients first treated with two-stage revision (p = 0.001). CONCLUSION: Infection control was better with two-stage revision than DAIR. The chance of eventual clearance of infection with limb preservation was better when two-stage revision was chosen as the initial treatment. However, the loss to follow-up in the two-stage revision group would likely make the true proportion of infection control lower than our estimate. Our experience would suggest that the process of infection eradication is a complex and difficult one. Most patients undergo multiple operations. Nearly one-third of patients eventually underwent amputation, and this was a serious risk for both groups. While we cannot strongly recommend one approach over the other based on our data, we would still consider the use of DAIR in patients who present with acute short duration of symptoms (< 3 weeks), no radiographic signs of erosion around fixed implants, and organisms other than Staphylococcus aureus. We would advocate the extended DAIR procedure with removal of all segmental or modular components, and we would caution patients that there is a high likelihood of needing further surgery. A prospective trial with strict adherence to indications may be needed to evaluate the relative merits of an extended DAIR procedure versus a two-stage revision. LEVEL OF EVIDENCE: Level III, therapeutic study.

BIGH3 mediates apoptosis and gap junction failure in osteocytes during renal cell carcinoma bone metastasis progression.

Renal cell carcinoma (RCC) bone metastatis progression is driven by crosstalk between tumor cells and the bone microenvironment, which includes osteoblasts, osteoclasts, and osteocytes. RCC bone metastases (RCCBM) are predominantly osteolytic and resistant to antiresorptive therapy. The molecular mechanisms underlying pathologic osteolysis and disruption of bone homeostasis remain incompletely understood. We previously reported that BIGH3/TGFBI (transforming growth factor-beta-induced protein ig-h3, shortened to BIGH3 henceforth) secreted by colonizing RCC cells drives osteolysis by inhibiting osteoblast differentiation, impairing healing of osteolytic lesions, which is reversible with osteoanabolic agents. Here, we report that BIGH3 induces osteocyte apoptosis in both human RCCBM tissue specimens and in a preclinical mouse model. We also demonstrate that BIGH3 reduces Cx43 expression, blocking gap junction (GJ) function and osteocyte network communication. BIGH3-mediated GJ inhibition is blocked by the lysosomal inhibitor hydroxychloroquine (HCQ), but not osteoanabolic agents. Our results broaden the understanding of pathologic osteolysis in RCCBM and indicate that targeting the BIGH3 mechanism could be a combinational strategy for the treatment of RCCBM-induced bone disease that overcomes the limited efficacy of antiresorptives that target osteoclasts.

Percutaneous Cementation for Improvement of Pain and Function for Osteolytic Pelvic Metastasis: A Systematic Review.

INTRODUCTION: Pelvic metastasis is a common presentation among patients presenting with skeletal metastasis. Image-guided percutaneous cementation of these lesions is becoming increasingly popular for the treatment of these lesions. The objective of this study was to conduct a systematic review that investigates clinical outcomes after percutaneous cementation for pelvic metastasis. METHODS: A systematic review was registered with International Prospective Register of Systematic Reviews and performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using the PubMed, SCOPUS, and Ovid MEDLINE databases. All level I to IV clinical studies published in the English language investigating the clinical outcomes after percutaneous cementation for pelvic metastasis were included. RESULTS: Fourteen studies with 579 patients (278 men, 301 women) and 631 metastatic pelvic lesions were included in the study. The mean follow-up range was 0.7 to 26.4 months. Percutaneous cementation alone was performed in 441 patients (76.2%). Supplemental ablative procedures were performed in 77 patients (13.3%), and supplemental internal fixation using cannulated screws was performed in 107 patients (18.5%). Twelve studies with 430 patients (74.2%) reported pain-related and/or functional outcome scores, of which all studies reported overall clinically notable improvement at short-term follow-up. All studies reported periprocedural complications. Local cement leakage was the most common complication (162/631 lesions, 25.7%) followed by transient local pain (25/579 patients, 4.3%). There were no reported cases of major complications. Seven patients (1.2%) underwent re-intervention for persistent symptoms. CONCLUSIONS: Percutaneous cementation may be an effective method for treating pain and function related to pelvic metastasis. The most common complication was cement leakage surrounding the lesion. The rates of major complications were low, and most complications appeared minor and transient. Additional prospective studies are needed to further assess the efficacy of this procedure. LEVEL OF EVIDENCE: IV, systematic review of level I to IV therapeutic studies.

The risk of neurological deterioration while using neoadjuvant denosumab on patients with giant cell tumor of the spine presenting with epidural disease: a meta-analysis of the literature.

BACKGROUND CONTEXT: Giant cell tumor (GCT) of bone is most commonly a benign but locally aggressive primary bone tumor. Spinal GCTs account for 2.7% to 6.5% of all GCTs in bone. En bloc resection, which is the preferred treatment for GCT of the spine, may not always be feasible due to the location, extent of the tumor, and/or the patient's comorbidities. Neoadjuvant denosumab has recently been shown to be effective in downstaging GCT, decreasing the size and extent of GCTs. However, the risk of neurologic deterioration is of major concern for patients with epidural spinal cord compression due to spinal GCT. We experienced this concern when a patient presented to our institution with a midthoracic spinal GCT with progressive epidural disease. The patient was not a good surgical candidate due to severe cardiac disease and uncontrolled diabetes. In considering nonoperative management for this patient, we asked ourselves the following question: What is the risk that this patient will develop neurologic deterioration if we do not urgently operate and opt to treat him with denosumab instead? PURPOSE: The purpose of this study was to assess the literature to (1) determine the risk of neurological deterioration in patients receiving neoadjuvant denosumab for the treatment of spinal GCT and (2) to evaluate the secondary outcomes including radiographic features, surgical/technical complexity, and histological features after treatment. STUDY DESIGN/SETTING: Meta-analysis of the literature. PATIENT SAMPLE: Surgical cases of spinal GCT that (1) presented with type III Campanacci lesions, (2) had epidural disease classified as Bilsky type 1B or above and (3) received neoadjuvant denosumab therapy. OUTCOME MEASURES: The primary outcome measure of interest was neurologic status during denosumab treatment. Secondary outcome measures of interest included radiographic features, surgical/technical complexity, histological features, tumor recurrence, and metastasis. METHODS: Using predetermined inclusion and exclusion criteria, PubMed and Embase electronic databases were searched in August 2022 for articles reporting spinal GCTs treated with neoadjuvant denosumab and surgery. Keywords used were "Spine" AND "Giant Cell Tumor" AND "Denosumab." RESULTS: A total of 428 articles were identified and screened. A total of 22 patients from 12 studies were included for review. 17 patients were female (17/22, 77%), mean age was 32 years (18-62 years) and average follow-up was 21 months. Most GCTs occurred in the thoracic and thoracolumbar spine (11 patients, 50%), followed by 36% in the lumbar spine and 14% in the cervical spine. Almost half of the patients had neurological deficits at presentation (10/22 patients, 45%), and more than 60% had Bilsky 2 or 3 epidural spinal cord compression. None of the patients deteriorated neurologically, irrespective of their neurological status at presentation (p-value=.02, CI -2.58 to -0.18). There were no local recurrences reported. One patient was found to have lung nodules postoperatively. More than 90% of cases had decreased overall tumor size and increased bone formation. Surgical dissection was facilitated in more than 85% of those who had documented surgical procedures. Four patients (18%) underwent initial spinal stabilization followed by neoadjuvant denosumab and then surgical excision of the GCT. Regarding the histologic analyses, denosumab eradicated the giant cells in 95% of cases. However, residual Receptor Activator of Nuclear Factor Kappa B Ligand (RANKL)-positive stromal cells were noted, in 27% (6 cases). CONCLUSIONS: Neoadjuvant denosumab was a safe and effective means of treating spinal GCTs prior to surgery. Neurologic status remained stable or improved in all cases included in our review, irrespective of the presenting neurologic status. The most appropriate dosage and duration of denosumab therapy is yet to be determined. We recommend future well-designed studies to further evaluate the use of neoadjuvant denosumab for patients with spinal GCT.

A randomized, non-comparative phase 2 study of neoadjuvant immune-checkpoint blockade in retroperitoneal dedifferentiated liposarcoma and extremity/truncal undifferentiated pleomorphic sarcoma.

Based on the demonstrated clinical activity of immune-checkpoint blockade (ICB) in advanced dedifferentiated liposarcoma (DDLPS) and undifferentiated pleomorphic sarcoma (UPS), we conducted a randomized, non-comparative phase 2 trial ( NCT03307616 ) of neoadjuvant nivolumab or nivolumab/ipilimumab in patients with resectable retroperitoneal DDLPS (n = 17) and extremity/truncal UPS (+ concurrent nivolumab/radiation therapy; n = 10). The primary end point of pathologic response (percent hyalinization) was a median of 8.8% in DDLPS and 89% in UPS. Secondary end points were the changes in immune infiltrate, radiographic response, 12- and 24-month relapse-free survival and overall survival. Lower densities of regulatory T cells before treatment were associated with a major pathologic response (hyalinization > 30%). Tumor infiltration by B cells was increased following neoadjuvant treatment and was associated with overall survival in DDLPS. B cell infiltration was associated with higher densities of regulatory T cells before treatment, which was lost upon ICB treatment. Our data demonstrate that neoadjuvant ICB is associated with complex immune changes within the tumor microenvironment in DDLPS and UPS and that neoadjuvant ICB with concurrent radiotherapy has significant efficacy in UPS.

Multimodality Imaging for 3D Printing and Surgical Rehearsal in Complex Spine Surgery.

Surgery is the mainstay treatment of symptomatic spinal tumors. It aids in restoring functionality, managing pain and tumor growth, and improving overall quality of life. Over the past decade, advancements in medical imaging techniques combined with the use of three-dimensional (3D) printing technology have enabled improvements in the surgical management of spine tumors by significantly increasing the precision, accuracy, and safety of the surgical procedures. For complex spine surgical cases, the use of multimodality imaging is necessary to fully visualize the extent of disease, including both soft-tissue and bone involvement. Integrating the information provided by these examinations in a cohesive manner to facilitate surgical planning can be challenging, particularly when multiple surgical specialties work in concert. The digital 3-dimensional (3D) model or 3D rendering and the 3D printed model created from imaging examinations such as CT and MRI not only facilitate surgical planning but also allow the placement of virtual and physical surgical or osteotomy planes, further enhancing surgical planning and rehearsal. The authors provide practical information about the 3D printing workflow, from image acquisition to postprocessing of a 3D printed model, as well as optimal material selection and incorporation of quality management systems, to help surgeons utilize 3D printing for surgical planning. The authors also highlight the process of surgical rehearsal, how to prescribe digital osteotomy planes, and integration with intraoperative surgical navigation systems through a case-based discussion. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

Customized 3-dimensional-printed Vertebral Implants for Spinal Reconstruction After Tumor Resection: A Systematic Review.

STUDY DESIGN: Systematic review. OBJECTIVE: To examine the outcomes of customized 3-dimensional (3D) printed implants for spinal reconstruction after tumor resection. SUMMARY OF BACKGROUND DATA: Various techniques exist for spinal reconstruction after tumor resection. Currently, there is no consensus regarding the utility of customized 3D-printed implants for spinal reconstruction after tumor resection. MATERIALS AND METHODS: A systematic review was registered with PROSPERO and performed according to "Preferred Reporting Items for Systematic Reviews and Meta-analyses" guidelines. All level I-V evidence studies reporting the use of 3D-printed implants for spinal reconstruction after tumor resection were included. RESULTS: Eleven studies (65 patients; mean age, 40.9 ± 18.1 y) were included. Eleven patients (16.9%) underwent intralesional resections with positive margins and 54 patients (83.1%) underwent en bloc spondylectomy with negative margins. All patients underwent vertebral reconstruction with 3D-printed titanium implants. Tumor involvement was in the cervical spine in 21 patients (32.3%), thoracic spine in 29 patients (44.6%), thoracolumbar junction in 2 patients (3.1%), and lumbar spine in 13 patients (20.0%). Ten studies with 62 patients reported perioperative outcomes radiologic/oncologic status at final follow-up. At the mean final follow-up of 18.5 ± 9.8 months, 47 patients (75.8%) had no evidence of disease, 9 patients (14.5%) were alive with recurrence, and 6 patients (9.7%) had died of disease. One patient who underwent C3-C5 en bloc spondylectomy had an asymptomatic subsidence of 2.7 mm at the final follow-up. Twenty patients that underwent thoracic and/or lumbar reconstruction had a mean subsidence of 3.8 ± 4.7 mm at the final follow-up; however, only 1 patient had a symptomatic subsidence that required revision surgery. Eleven patients (17.7%) had one or more major complications. CONCLUSION: There is some evidence to suggest that using customized 3D-printed titanium or titanium alloy implants is an effective technique for spinal reconstruction after tumor resection. There is a high incidence of asymptomatic subsidence and major complications that are similar to other methods of reconstruction. LEVEL OF EVIDENCE: Level V, systematic review of level I-V studies.

Advances in Virtual Cutting Guide and Stereotactic Navigation for Complex Tumor Resections of the Sacrum and Pelvis: Case Series with Short-Term Follow-Up.

Primary malignancies of the sacrum and pelvis are aggressive in nature, and achieving negative margins is essential for preventing recurrence and improving survival after en bloc resections. However, these are particularly challenging interventions due to the complex anatomy and proximity to vital structures. Using virtual cutting guides to perform navigated osteotomies may be a reliable method for safely obtaining negative margins in complex tumor resections of the sacrum and pelvis. This study details the technique and presents short-term outcomes. Patients who underwent an en bloc tumor resection of the sacrum and/or pelvis using virtual cutting guides with a minimum follow-up of two years were retrospectively analyzed and included in this study. Preoperative computer-assisted design (CAD) was used to design osteotomies in each case. Segmentation, delineating the tumor from normal tissue, was performed by the senior author using preoperative CT scans and MRI. Working with a team of biomedical engineers, virtual surgical planning was performed to create osteotomy lines on the preoperative CT and overlaid onto the intraoperative CT. The pre-planned osteotomy lines were visualized as "virtual cutting guides" providing real-time stereotactic navigation. A precision ultrasound-powered cutting tool was then integrated into the navigation system and used to perform the osteotomies in each case. Six patients (mean age 52.2 ± 17.7 years, 2 males, 4 females) were included in this study. Negative margins were achieved in all patients with no intraoperative complications. Mean follow-up was 38.0 ± 6.5 months (range, 24.8-42.2). Mean operative time was 1229 min (range, 522-2063). Mean length of stay (LOS) was 18.7 ± 14.5 days. There were no cases of 30-day readmissions, 30-day reoperations, or 2-year mortality. One patient was complicated by flap necrosis, which was successfully treated with irrigation and debridement and primary closure. One patient had local tumor recurrence at final follow-up and two patients are currently undergoing treatment for metastatic disease. Using virtual cutting guides to perform navigated osteotomies is a safe technique that can facilitate complex tumor resections of the sacrum and pelvis.

The Use of Photodynamic Bone Stabilization to Tamponade Bleeding in a Pathologic Humeral Shaft Fracture: A Case Report.

Introduction: Hypervascular tumors such as renal and thyroid carcinoma have a significant risk of intraoperative bleeding. To help mitigate bleeding, interventional preoperative embolization is traditionally used; however, it is success is highly variable. This is the first case report to discuss using expandable balloon implants with a minimally invasive approach to achieve fracture fixation and tamponade acute intraoperative bleeding. Case Report: A 48-year-old male with clear-cell renal cell carcinoma presented with a left humeral shaft pathologic fracture. The patient was scheduled to undergo open biopsy, curettage of tumor, and fracture fixation with an intramedullary device. Intraoperatively, during open biopsy and curettage, brisk bleeding was encountered, which ceased after inserting an intramedullary photodynamic bone stabilization implant (IlluminOss). The implant's balloon expanded to the diameter of the humerus allowing for tamponade, fracture stability, and a minimally invasive approach. Conclusion: We present a possible intraoperative option for achieving control of bleeding in pathologic long bone fractures by deploying a photodynamic stabilization device. The method described can have applications in specific patients and obviate the need for pre-operative embolization for highly vascular tumors due to the implant's ability to create tamponade within the bone.

What Is the Prosthetic Survival After Resection and Intercalary Endoprosthetic Reconstruction for Diaphyseal Bone Metastases of the Humerus and Femur?

BACKGROUND: Large metastatic lesions of the diaphysis can cause considerable pain and result in difficult surgical challenges. Resection and cemented intercalary endoprosthetic reconstruction offer one solution to the problem, but it is an extensive operation that might not be tolerated well by a debilitated patient. The risk of aseptic loosening and revision after intercalary endoprosthetic replacement has varied in previous reports, which have not examined the risk of revision in the context of patient survival. QUESTIONS/PURPOSES: (1) In a small case series from one institution, what is the survivorship of patients after cemented intercalary endoprosthetic replacement for diaphyseal metastasis, and what is the cumulative incidence of revision for any reason? (2) What are the complications associated with cemented intercalary reconstruction? (3) What is the functional outcome after the procedure as assessed by the MSTS93 score? METHODS: We retrospectively studied 19 patients with diaphyseal long bone metastases who were treated with resection and cemented intercalary endoprosthetic reconstruction by five participating surgeons at one referral center from 2006 to 2017. There were 11 men and eight women with a median age of 59 years (range 46 to 80 years). The minimum follow-up required for this series was 12 months; however, patients who reached an endpoint (death, radiographic loosening, or implant revision) before that time were included. One of these 19 patients was lost to follow-up but was not known to have died. The median follow-up was 24 months (range 0 to 116 months). Eight of the 19 patients presented with pathologic fractures. Ten of 19 lesions involved the femur, and nine of 19 were in the humerus. The most common pathologic finding was renal cell carcinoma (in 10 of 19). Survival estimates of the patients were calculated using the Kaplan-Meier method. A competing risks estimator was used to evaluate implant survival, using death of the patient as the competing risk. We also estimated the cumulative incidence of aseptic loosening in a competing risk analysis. Radiographs were analyzed for radiolucency at the bone-cement-implant interfaces, fracture, integrity of the cement mantle, and component position stability. Complications were assessed using record review that was performed by an individual who was not involved in the initial care of the patients. Functional outcomes were assessed using the MSTS93 scoring system. RESULTS: Patient survivorship was 68% (95% CI 50% to 93%) at 1 year, 53% (95% CI 34% to 81%) at 2 years, and 14% (95% CI 4% to 49%) at 5 years; the median patient survival time after reconstruction was 25 months (range 0 to 116 months). In the competing risk analysis, using death as the competing risk, the cumulative incidence of implant revision was 11% (95% CI 2% to 29%) at 1 year and 16% (95% CI 4% to 36%) at 5 years after surgery; however, the cumulative incidence of aseptic loosening (with death as a competing risk) was 22% (95% CI 6% to 43%) at 1 year and 33% (95% CI 13% to 55%) at 5 years after surgery. Other complications included one patient who died postoperatively of cardiac arrest, one patient with delayed wound healing, two patients with bone recurrence, and one patient who experienced local soft tissue recurrence that was excised without implant revision. Total MSTS93 scores improved from a mean of 12.6 ± 8.1 (42% ± 27%) preoperatively to 21.5 ± 5.0 (72% ± 17%) at 3 months postoperatively (p < 0.001) and 21.6 ± 8.5 (72% ± 28%) at 2 years postoperatively (p = 0.98; 3 months versus 2 years). CONCLUSION: Resection of diaphyseal metastases with intercalary reconstruction can provide stability and short-term improvement in function for patients with advanced metastatic disease and extensive cortical destruction. Aseptic loosening is a concern, particularly in the humerus; however, the competing risk analysis suggests the procedure is adequate for most patients, because many in this series died of disease without undergoing revision. LEVEL OF EVIDENCE: Level IV, therapeutic study .

Risk factors for sacral fracture following en bloc chordoma resection.

OBJECTIVE: The purpose of this study was to analyze risk factors for sacral fracture following noninstrumented partial sacral amputation for en bloc chordoma resection. METHODS: A multicenter retrospective chart review identified patients who underwent noninstrumented partial sacral amputation for en bloc chordoma resection with pre- and postoperative imaging. Hounsfield units (HU) were measured in the S1 level. Sacral amputation level nomenclature was based on the highest sacral level with bone removed (e.g., S1 foramen amputation at the S1-2 vestigial disc is an S2 sacral amputation). Variables collected included basic demographics, patient comorbidities, surgical approach, preoperative radiographic details, neoadjuvant and adjuvant radiation therapy, and postoperative sacral fracture data. RESULTS: A total of 101 patients (60 men, 41 women) were included; they had an average age of 69 years, BMI of 29 kg/m2, and follow-up of 60 months. The sacral amputation level was S1 (2%), S2 (37%), S3 (44%), S4 (9%), and S5 (9%). Patients had a posterior-only approach (77%) or a combined anterior-posterior approach (23%), with 10 patients (10%) having partial sacroiliac (SI) joint resection. Twenty-seven patients (27%) suffered a postoperative sacral fracture, all occurring between 1 and 7 months after the index surgery. Multivariable logistic regression analysis demonstrated S1 or S2 sacral amputation level (p = 0.001), combined anterior-posterior approach (p = 0.0064), and low superior S1 HU (p = 0.027) to be independent predictors of sacral fracture. The fracture rate for patients with superior S1 HU < 225, 225-300, and > 300 was 38%, 15%, and 9%, respectively. An optimal superior S1 HU cutoff of 300 was found to maximize sensitivity (89%) and specificity (42%) in predicting postamputation sacral fracture. In addition, the fracture rate for patients who underwent partial SI joint resection was 100%. CONCLUSIONS: Patients with S1 or S2 partial sacral amputations, a combined anterior-posterior surgical approach, low superior S1 HU, and partial SI joint resection are at higher risk for postoperative sacral fracture following en bloc chordoma resection and should be considered for spinopelvic instrumentation at the index procedure.

Practice Pattern Variability in the Management of Regional Lymph Node Metastasis in Extremity and Trunk Soft Tissue Sarcoma: A Survey of the Society of Surgical Oncology and Musculoskeletal Tumor Society Membership.

BACKGROUND: Regional lymph node metastasis in extremity and trunk soft tissue sarcoma (ETSTS) is rare with no standardized management. We sought to determine management patterns for regional lymph node metastasis in ETSTS. METHODS: A survey regarding the management of ETSTS lymph node metastasis was distributed to the membership of the Musculoskeletal Tumor Society (MSTS) and the Society of Surgical Oncology (SSO) in January 2022. The survey queried the type of training (surgical oncology, orthopedic oncology), details of their practice setting, and management decisions of hypothetical ETSTS scenarios that involved potential or confirmed lymph node metastasis. RESULTS: The survey was distributed to 349 MSTS members (open rate of 63%, completion rate 21%) and 3026 SSO members (open rate of 55%, completion rate 4.7%) and was completed by 214 respondents, of whom 73 (34.1%) and 141 (65.9%) were orthopedic oncology and surgical oncology fellowship-trained, respectively. The majority of respondents practiced in an academic setting (n = 171, 79.9%) and treat >10 extremity sarcoma cases annually (n = 138, 62.2%). In scenarios with confirmed nodal disease for clear cell and epithelioid sarcoma, surgical oncologists were inclined to perform lymphadenectomy, while orthopedic oncologists were inclined to offer targeted lymph node excision with adjuvant radiation (p < 0.001). There was heterogeneity of responses regarding the management of nodal disease regardless of training background. CONCLUSION: Self-reported management of nodal disease in ETSTS was variable among respondent groups with differences and similarities based on training background. These data highlight the variability of practice for nodal disease management and the need for consensus-based guidelines.

Hypofractionated, 3-week, preoperative radiotherapy for patients with soft tissue sarcomas (HYPORT-STS): a single-centre, open-label, single-arm, phase 2 trial.

BACKGROUND: The standard preoperative radiotherapy regimen of 50 Gy delivered in 25 fractions for 5 weeks for soft tissue sarcomas results in excellent local control, with major wound complications occurring in approximately 35% of patients. We aimed to investigate the safety of a moderately hypofractionated, shorter regimen of radiotherapy, which could be more convenient for patients. METHODS: This single-centre, open-label, single-arm, phase 2 trial (HYPORT-STS) was done at a single tertiary cancer care centre (MD Anderson Cancer Center, Houston, TX, USA). We administered preoperative radiotherapy to a dose of 42·75 Gy in 15 fractions of 2·85 Gy/day for 3 weeks (five fractions per week) to adults (aged ≥18 years) with non-metastatic soft tissue sarcomas of the extremities or superficial trunk and an Eastern Cooperative Oncology Group performance status of 0-3. The primary endpoint was a major wound complication occurring within 120 days of surgery. Major wound complications were defined as those requiring a secondary operation, or operations, under general or regional anaesthesia for wound treatment; readmission to the hospital for wound care; invasive procedures for wound care; deep wound packing to an area of wound measuring at least 2 cm in length; prolonged dressing changes; repeat surgery for revision of a split thickness skin graft; or wet dressings for longer than 4 weeks. We analysed our primary outcome and safety in all patients who enrolled. We monitored safety using a Bayesian, one-arm, time-to-event stopping rule simulator comparing the rate of major wound complications at 120 days post-surgery among study participants with the historical rate of 35%. This trial is registered with ClinicalTrials.gov, NCT03819985, recruitment is complete, and follow-up continues. FINDINGS: Between Dec 18, 2018, and Jan 6, 2021, we assessed 157 patients for eligibility, of whom 120 were enrolled and received hypofractionated preoperative radiotherapy. At no time did the stopping rule computation indicate that the trial should be stopped early for lack of safety. Median postoperative follow-up was 24 months (IQR 17-30). Of 120 patients, 37 (31%, 95% CI 24-40) developed a major wound complication at a median time of 37 days (IQR 25-59) after surgery. No patient had acute radiation toxicity (during radiotherapy or within 4 weeks of the radiotherapy end date) of grade 3 or worse (Common Terminology Criteria for Adverse Events [CTCAE] version 4.0) or an on-treatment serious adverse event. Four (3%) of 115 patients had late radiation toxicity (≥6 months post-surgery) of at least grade 3 (CTCAE or Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer Late Radiation Morbidity Scoring Scheme): femur fractures (n=2), lymphoedema (n=1), and skin ulceration (n=1). There were no treatment-related deaths. INTERPRETATION: Moderately hypofractionated preoperative radiotherapy delivered to patients with soft tissue sarcomas was safe and could therefore be a more convenient alternative to conventionally fractionated radiotherapy. Patients can be counselled about these results and potentially offered this regimen, particularly if it facilitates care at a sarcoma specialty centre. Results on long-term oncological, late toxicity, and functional outcomes are awaited. FUNDING: The National Cancer Institute.

Osteoid Tumors of Bone.

We present a review of several bone (osteoid)-forming tumors including enostosis, osteoid osteoma, osteoblastoma, and osteosarcoma. These entities were chosen because they are reasonably common-neither seen every day nor rare. When applicable, recent information about the lesions is included.