Active surveillance of diffuse-type tenosynovial giant cell tumors: A retrospective, multicenter cohort study.

BACKGROUND: Diffuse-type tenosynovial giant cell tumor (D-TGCT) is a mono-articular, soft-tissue tumor. Although it can behave locally aggressively, D-TGCT is a non-malignant disease. This is the first study describing the natural course of D-TGCT and evaluating active surveillance as possible treatment strategy. METHODS: This retrospective, multicenter study included therapy naïve patients with D-TGCT from eight sarcoma centers worldwide between 2000 and 2019. Patients initially managed by active surveillance following their first consultation were eligible. Data regarding the radiological and clinical course and subsequent treatments were collected. RESULTS: Sixty-one patients with primary D-TGCT were initially managed by active surveillance. Fifty-nine patients had an MRI performed around first consultation: D-TGCT was located intra-articular in most patients (n = 56; 95 %) and extra-articular in 14 cases (24 %). At baseline, osteoarthritis was observed in 13 patients (22 %) on MRI. Most of the patients' reported symptoms: pain (n = 43; 70 %), swelling (n = 33; 54 %). Eight patients (13 %) were asymptomatic. Follow-up data were available for 58 patients; the median follow-up was 28 months. Twenty-one patients (36 %) had radiological progression after 21 months (median). Eight of 45 patients (18 %) without osteoarthritis at baseline developed osteoarthritis during follow-up. Thirty-seven patients (64 %) did not clinically deteriorate during follow-up. Finally, eighteen patients (31 %) required a subsequent treatment. CONCLUSION: Active surveillance can be considered adequate for selected therapy naïve D-TGCT patients. Although follow-up data was limited, almost two-thirds of the patients remained progression-free, and 69 % did not need treatment during the follow-up period. However, one-fifth of patients developed secondary osteoarthritis. Prospective studies on active surveillance are warranted.

Use of virtual reality for the management of phantom limb pain: a systematic review.

PURPOSE: To summarize the research on the effectiveness of virtual reality (VR) therapy for the management of phantom limb pain (PLP). METHODS: Three databases (SCOPUS, Ovid Embase, and Ovid MEDLINE) were searched for studies investigating the use of VR therapy for the treatment of PLP. Original research articles fulfilling the following criteria were included: (i) patients 18 years and older; (ii) all etiologies of amputation; (iii) any level of amputation; (iv) use of immersive VR as a treatment modality for PLP; (v) self-reported objective measures of PLP before and after at least one VR session; (vi) written in English. RESULTS: A total of 15 studies were included for analysis. Fourteen studies reported decreases in objective pain scores following a single VR session or a VR intervention consisting of multiple sessions. Moreover, combining VR with tactile stimulation had a larger beneficial effect on PLP compared with VR alone. CONCLUSIONS: Based on the current literature, VR therapy has the potential to be an effective treatment modality for the management of PLP. However, the low quality of studies, heterogeneity in subject population and intervention type, and lack of data on long-term relief make it difficult to draw definitive conclusions.IMPLICATION FOR REHABILITATIONVirtual reality (VR) therapy has emerged as a new potential treatment option for phantom limb pain (PLP) that circumvents some limitations of mirror therapy.VR therapy was shown to decrease PLP following a single VR session as well as after an intervention consisting of multiple sessions.The addition of vibrotactile stimuli to VR therapy may lead to larger decreases in PLP scores compared with VR therapy alone.

Reconstruction following oncological iliosacral resection.

Aims: The sacroiliac joint (SIJ) is the only mechanical connection between the axial skeleton and lower limbs. Following iliosacral resection, there is debate on whether reconstruction of the joint is necessary. There is a paucity of data comparing the outcomes of patients undergoing reconstruction and those who are not formally reconstructed. Methods: A total of 60 patients (25 females, 35 males; mean age 39 years (SD 18)) undergoing iliosacral resection were reviewed. Most resections were performed for primary malignant tumours (n = 54; 90%). The mean follow-up for surviving patients was nine years (2 to 19). Results: Overall, 27 patients (45%) were reconstructed, while 33 (55%) had no formal reconstruction. There was no difference in the use of chemotherapy (p = 1.000) or radiotherapy (p = 0.292) between the groups. Patients with no reconstruction had a mean larger tumour (11 cm (SD 5) vs 8 cm (SD 4); p = 0.014), mean shorter operating times (664 mins (SD 195) vs 1,324 mins (SD 381); p = 0.012), and required fewer blood units (8 (SD 7) vs 14 (SD 11); p = 0.012). Patients undergoing a reconstruction were more likely to have a deep infection (48% vs 12%; p = 0.003). Nine reconstructed patients had a hardware failure, with five requiring revision. Postoperatively 55 (92%) patients were ambulatory, with no difference in the proportion of ambulatory patients (89% vs 94%; p = 0.649) or mean Musculoskeletal Tumor Society Score (59% vs 65%; p = 0.349) score between patients who did or did not have a reconstruction. The ten-year disease-specific survival was 69%, with no difference between patients who were reconstructed and those who were not (78% vs 45%; p = 0.316). There was no difference in the rate of metastasis between the two groups (hazard ratio (HR) 2.78; p = 0.102). Conclusion: Our results demonstrate that SIJ reconstruction is associated with longer operating times, greater need for blood transfusion, and more postoperative infections, without any improvement in functional outcomes when compared to patients who did not have formal SIJ reconstruction.

Genetically inferred birthweight, height, and puberty timing and risk of osteosarcoma.

INTRODUCTION: Several studies have linked increased risk of osteosarcoma with tall stature, high birthweight, and early puberty, although evidence is inconsistent. We used genetic risk scores (GRS) based on established genetic loci for these traits and evaluated associations between genetically inferred birthweight, height, and puberty timing with osteosarcoma. METHODS: Using genotype data from two genome-wide association studies, totaling 1039 cases and 2923 controls of European ancestry, association analyses were conducted using logistic regression for each study and meta-analyzed to estimate pooled odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses were conducted by case diagnosis age, metastasis status, tumor location, tumor histology, and presence of a known pathogenic variant in a cancer susceptibility gene. RESULTS: Genetically inferred higher birthweight was associated with an increased risk of osteosarcoma (OR =1.59, 95% CI 1.07-2.38, P = 0.02). This association was strongest in cases without metastatic disease (OR =2.46, 95% CI 1.44-4.19, P = 9.5 ×10-04). Although there was no overall association between osteosarcoma and genetically inferred taller stature (OR=1.06, 95% CI 0.96-1.17, P = 0.28), the GRS for taller stature was associated with an increased risk of osteosarcoma in 154 cases with a known pathogenic cancer susceptibility gene variant (OR=1.29, 95% CI 1.03-1.63, P = 0.03). There were no significant associations between the GRS for puberty timing and osteosarcoma. CONCLUSION: A genetic propensity to higher birthweight was associated with increased osteosarcoma risk, suggesting that shared genetic factors or biological pathways that affect birthweight may contribute to osteosarcoma pathogenesis.

Open Versus Core Needle Biopsy in Lower-Extremity Sarcoma: Current Practice Patterns and Patient Outcomes.

BACKGROUND: Historically, open biopsy (OB) was the gold standard for sarcoma diagnosis. Core needle biopsy (CNB) has become increasingly common. There are limited data evaluating how the type of biopsy impacts definitive surgical resection or postoperative outcomes. The aims of this study were to (1) characterize current international biopsy practice patterns, and (2) evaluate how the type of biopsy performed impacts the resection surgery, infection risk, oncological complications, and patient-reported functional outcome scores. METHODS: This study was a preplanned secondary analysis of the prospective, multicenter PARITY (Prophylactic Antibiotic Regimens in Tumor Surgery) study. Patients with a benign diagnosis, metastatic disease, or no biopsy prior to surgery were excluded. Prospectively collected demographic, biopsy, surgical, and outcome variables were analyzed, and differences between patients undergoing OB and CNB were assessed. Parametric and nonparametric tests were used to compare variables between groups, and the Cox proportional hazards method was used to compare infection-related and oncological outcomes at 1 year. Median functional outcome scores at 1 year were compared. RESULTS: Four hundred and sixty-four patients met the inclusion criteria. Data were collected from 48 sarcoma centers in 12 countries. CNB was the more utilized biopsy modality overall (57.5%). OB was more common in the U.S. and Canada. The median operative time was significantly longer for patients who underwent OB (324 versus 260 minutes; p < 0.001). Significantly more skin (p < 0.001) and fascial tissue (p < 0.001) were excised in the OB group, which also had a lower rate of primary closure (86.3% versus 92.9%; p = 0.03). There were no differences in surgical site infection or oncological outcomes between the groups at 1-year follow-up. CONCLUSIONS: CNB was the more common biopsy modality in the PARITY study in most countries. However, OB was more common in the U.S. and Canada. Patients undergoing OB had longer operative times, more excised tissue, and lower rates of primary closure, but this did not translate to differences in infection rates or oncological outcomes, including local recurrence. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Mutant IDH regulates glycogen metabolism from early cartilage development to malignant chondrosarcoma formation.

Chondrosarcomas are the most common malignancy of cartilage and are associated with somatic mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 genes. Somatic IDH mutations are also found in its benign precursor lesion, enchondromas, suggesting that IDH mutations are early events in malignant transformation. Human mutant IDH chondrosarcomas and mutant Idh mice that develop enchondromas investigated in our studies display glycogen deposition exclusively in mutant cells from IDH mutant chondrosarcomas and Idh1 mutant murine growth plates. Pharmacologic blockade of glycogen utilization induces changes in tumor cell behavior, downstream energetic pathways, and tumor burden in vitro and in vivo. Mutant IDH1 interacts with hypoxia-inducible factor 1α (HIF1α) to regulate expression of key enzymes in glycogen metabolism. Here, we show a critical role for glycogen in enchondromas and chondrosarcomas, which is likely mediated through an interaction with mutant IDH1 and HIF1α.

Is a radiological score able to predict resection-grade chondrosarcoma in primary intraosseous lesions of the long bones?

Aims: The preoperative grading of chondrosarcomas of bone that accurately predicts surgical management is difficult for surgeons, radiologists, and pathologists. There are often discrepancies in grade between the initial biopsy and the final histology. Recent advances in the use of imaging methods have shown promise in the ability to predict the final grade. The most important clinical distinction is between grade 1 chondrosarcomas, which are amenable to curettage, and resection-grade chondrosarcomas (grade 2 and 3) which require en bloc resection. The aim of this study was to evaluate the use of a Radiological Aggressiveness Score (RAS) to predict the grade of primary chondrosarcomas in long bones and thus to guide management. Methods: A total of 113 patients with a primary chondrosarcoma of a long bone presenting between January 2001 and December 2021 were identified on retrospective review of a single oncology centre's prospectively collected database. The nine-parameter RAS included variables from radiographs and MRI scans. The best cut-off of parameters to predict the final grade of chondrosarcoma after resection was determined using a receiver operating characteristic curve (ROC), and this was correlated with the biopsy grade. Results: A RAS of ≥ four parameters was 97.9% sensitive and 90.5% specific in predicting resection-grade chondrosarcoma based on a ROC cut-off derived using the Youden index. Cronbach's α of 0.897 was derived as the interclass correlation for scoring the lesions by four blinded reviewers who were surgeons. Concordance between resection-grade lesions predicted from the RAS and ROC cut-off with the final grade after resection was 96.46%. Concordance between the biopsy grade and the final grade was 63.8%. However, when the patients were analyzed based on surgical management, the initial biopsy was able to differentiate low-grade from resection-grade chondrosarcomas in 82.9% of biopsies. Conclusion: These findings suggest that the RAS is an accurate method for guiding the surgical management of patients with these tumours, particularly when the initial biopsy results are discordant with the clinical presentation.

Giant cell tumour of bone.

Giant cell tumour of bone (GCTB) is a locally aggressive lesion that is difficult to treat as salvaging the joint can be associated with a high rate of local recurrence (LR). We evaluated the risk factors for tumour relapse after treatment of a GCTB of the limbs. A total of 354 consecutive patients with a GCTB underwent joint salvage by curettage and reconstruction with bone graft and/or cement or en bloc resection. Patient, tumour, and treatment factors were analyzed for their impact on LR. Patients treated with denosumab were excluded. There were 53 LRs (15%) at a mean 30.5 months (5 to 116). LR was higher after curettage (18.4%) than after resection (4.6%; p = 0.008). Neither pathological fracture (p = 0.240), Campanacci grade (p = 0.734), soft-tissue extension (p = 0.297), or tumour size (p = 0.872) affected the risk of recurrence. Joint salvage was possible in 74% of patients overall (262/354), and 98% after curettage alone (262/267). Of 49 patients with LR after curettage, 44 (90%) underwent repeated curettage and joint salvage. For patients treated by curettage, only age less than 30 years (p = 0.042) and location in the distal radius (p = 0.043) predicted higher LR. The rate of LR did not differ whether cement or bone graft was used (p = 0.753), but may have been reduced by the use of hydrogen peroxide (p = 0.069). Complications occurred in 15.3% of cases (54/354) and did not differ by treatment. Most patients with a GCTB can undergo successful joint salvage by aggressive curettage, even in the presence of a soft-tissue mass, pathological fracture, or a large lesion, with an 18.4% risk of local recurrence. However, 90% of local relapses after curettage can be treated by repeat joint salvage. Maximizing joint salvage is important to optimize long-term function since most patients with a GCTB are young adults. Younger patients and those with distal radius tumours treated with joint-sparing procedures have a higher rate of local relapse and may require more aggressive treatment and closer follow-up.

One-Stage Synovectomies Result in Improved Short-Term Outcomes Compared to Two-Stage Synovectomies of Diffuse-Type Tenosynovial Giant Cell Tumor (D-TGCT) of the Knee: A Multicenter, Retrospective, Cohort Study.

Diffuse-type tenosynovial giant cell tumors' (D-TGCTs) intra- and extra-articular expansion about the knee often necessitates an anterior and posterior surgical approach to facilitate an extensive synovectomy. There is no consensus on whether two-sided synovectomies should be performed in one or two stages. This retrospective study included 191 D-TGCT patients from nine sarcoma centers worldwide to compare the postoperative short-term outcomes between both treatments. Secondary outcomes were rates of radiological progression and subsequent treatments. Between 2000 and 2020, 117 patients underwent one-stage and 74 patients underwent two-stage synovectomies. The maximum range of motion achieved within one year postoperatively was similar (flexion 123-120°, p = 0.109; extension 0°, p = 0.093). Patients undergoing two-stage synovectomies stayed longer in the hospital (6 vs. 4 days, p < 0.0001). Complications occurred more often after two-stage synovectomies, although this was not statistically different (36% vs. 24%, p = 0.095). Patients treated with two-stage synovectomies exhibited more radiological progression and required subsequent treatments more often than patients treated with one-stage synovectomies (52% vs. 37%, p = 0.036) (54% vs. 34%, p = 0.007). In conclusion, D-TGCT of the knee requiring two-side synovectomies should be treated by one-stage synovectomies if feasible, since patients achieve a similar range of motion, do not have more complications, but stay for a shorter time in the hospital.

A Size-Based Criteria for Flap Reconstruction After Thigh-Adductor, Soft-Tissue Sarcoma Resection.

BACKGROUND: Resection of soft-tissue sarcomas from the adductor compartment is associated with significant complications. Free/pedicled flaps often are used for wound closure, but their effect on healing is unclear. We compared wound complications, oncologic, and functional outcomes for patients undergoing flap reconstruction or primary closure following resection of adductor sarcomas. METHODS: A total of 177 patients underwent resection of an adductor sarcoma with primary closure (PrC) or free/pedicled flap reconstruction (FR). Patient, tumor, and treatment characteristics were compared, as well as wound complications, oncologic, and functional outcomes (TESS/MSTS87/MSTS93). To examine the relative benefit of flap reconstruction, number needed to treat (NNT) was calculated. RESULTS: In total, 143 patients underwent PrC and 34 had FR, 68% of which were pedicled. There were few differences in demographic, tumor, or treatment characteristics. No significant difference was found in the rate of wound complications. Length of stay was significantly longer in FR (18 days vs. PrC 8 days; p < 0.01). Oncologic and functional outcomes were similar over 5 years follow-up. Uncomplicated wound healing occurred more often in FR compared with PrC for tumors with ≥15 cm (NNT = 8.4) or volumes ≥ 800 ml (NNT = 8.4). Tumors ≤ 336 ml do not benefit from a flap, whereas those > 600 ml are 1.5 times more likely to heal uneventfully after flap closure. CONCLUSIONS: Although flap use prolonged hospitalization, it decreased wound healing complications for larger tumors, and in all sized tumors, it demonstrated similar functional and oncologic outcomes to primary closure. Our size-based treatment criteria can help to identify patients with large adductor sarcomas who could benefit from flap reconstruction. LEVEL OF EVIDENCE III: (Retrospective cohort study).

Outcome After Surgical Treatment of Dermatofibrosarcoma Protuberans (DFSP): Does it Require Extensive Follow-up and What is an Adequate Resection Margin?

INTRODUCTION: Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous tumour of indeterminate malignant potential. The mainstay treatment for DFSP is surgical resection. Given the reported high local recurrence rate, the ideal resection margin for DFSP is unclear. The purpose of this study was to ascertain the local recurrence and metastatic rate of DFSP and DFSP with fibrosarcomatous degeneration (FS-DFSP), with specific attention to margin status in an attempt to address the issue of margin adequacy. METHODS: Patients treated for DFSP at a single sarcoma centre were identified from a prospective database. DFSP and FS-DFSP patients with and without prior surgery were included. Patients were followed after surgery to monitor complications, local recurrence and metastasis. RESULTS: The study included 200 patients: 166 patients with DFSP and 34 patients with FS-DFSP. In the DFSP group, nine patients (5.4%) had positive margins, one case (0.6%) developed local recurrence (LR) and no patients developed distant metastases. In the FS-DFSP group, seven patients (20.6%) had positive margins, six patients (17.6%) developed local recurrence (LR) and eight patients (23.5%) developed distant metastases, of which three (37.5%) were in the lungs, one (12.5%) in bone and four (50%) in other soft tissue sites. DISCUSSION AND CONCLUSION: Local recurrence and metastases are extremely rare in patients with DFSP. Achieving a negative as opposed to a wide surgical margin may be sufficient to avoid local recurrence of most DFSP. We suggest that no ongoing surveillance for local or systemic relapse is required for DFSP patients after negative margin resection. For FS-DFSP, we recommend the same surveillance schedule, based on tumour grade, as other soft tissue sarcoma.

T2-weighted MRI radiomics in high-grade intramedullary osteosarcoma: predictive accuracy in assessing histologic response to chemotherapy, overall survival, and disease-free survival.

OBJECTIVE: To analyze radiomic features obtained from pre-treatment T2-weighted MRI acquisitions in patients with histologically proven intramedullary high-grade osteosarcomas and assess the accuracy of radiomic modelling as predictive biomarker of tumor necrosis following neoadjuvant chemotherapy (NAC), overall survival (OS), and disease-free survival (DFS). MATERIALS AND METHODS: Pre-treatment MRI exams in 105 consecutive patients who underwent NAC and resection of high-grade intramedullary osteosarcoma were evaluated. Histologic necrosis following NAC, and clinical outcome-survival data was collected for each case. Radiomic features were extracted from segmentations performed by two readers, with poorly reproducible features excluded from further analysis. Cox proportional hazard model and Spearman correlation with multivariable modelling were used for assessing relationships of radiomics features with OS, DFS, and histologic tumor necrosis. RESULTS: Study included 74 males, 31 females (mean 32.5yrs, range 15-77 years). Histologic assessment of tumor necrosis following NAC was available in 104 cases, with good response (≥ 90% necrosis) in 41, and poor response in 63. Fifty-three of 105 patients were alive at follow-up (median 40 months, range: 2-213 months). Median OS was 89 months. Excluding 14 patients with metastases at presentation, median DFS was 19 months. Eleven radiomics features were employed in final radiomics model predicting histologic tumor necrosis (mean AUC 0.708 ± 0.046). Thirteen radiomic features were used in model predicting OS (mean concordance index 0.741 ± 0.011), and 12 features retained in predicting DFS (mean concordance index 0.745 ± 0.010). CONCLUSIONS: T2-weighted MRI radiomic models demonstrate promising results as potential prognostic biomarkers of prospective tumor response to neoadjuvant chemotherapy and prediction of clinical outcomes in conventional osteosarcoma.

Intermuscular extremity myxoid liposarcoma can be managed by marginal resection following neoadjuvant radiotherapy.

BACKGROUND: Compared with other soft tissue sarcomas, myxoid liposarcoma (MLS) occurs in younger patients, has a propensity for intermuscular locations and is highly radiosensitive. With pre-operative radiotherapy, intermuscular MLS demonstrates substantial volume reduction and can be easily separated from surrounding tissues during resection. However, it is unclear whether marginal excision of MLS is oncologically safe. This study aimed to assess the association between margins and survival in irradiated, intermuscular MLS. METHODS: The study identified 198 patients from seven sarcoma centres with a first presentation of localized, extremity, intermuscular MLS that received pre-operative radiotherapy and was diagnosed between 1990 and 2017. Patient and treatment characteristics, radiological and histological responses to neoadjuvant treatment and clinical surveillance were recorded. RESULTS: Margins were microscopically positive in 11% (n = 22), <1.0 mm in 15% (n = 29) and ≥1.0 mm in 72% (n = 143). There was no association between margin status and local recurrence-free, metastasis-free or overall survival. This finding held true even in patients at higher risk of worse overall survival based on multivariable analysis (% round cell≥5%, percentage ellipsoid tumour volume change ≤ -60.1%). CONCLUSION: Irradiated, extremity, intermuscular myxoid liposarcoma can safely undergo marginal resection without compromising oncologic control.

Reconstructive Allograft Preparation for Long Bone Intercalary Segments After Tumor Resections: Toronto Sarcoma Protocol.

Background: The Reconstructive Allograft Preparation by Toronto Sarcoma (RAPTORS) protocol is reliable and reproducible without substantially adding to the surgical reconstruction time or cost. Our technique includes clearance of debris, lavage of the medullary canal, pressurized filling of the medullary canal with antibiotic-laden cement for its mechanical and antimicrobial properties, and insertion of cancellous autograft at the allograft-host junctional ends prior to dual-plate compression to fix the allograft into the defect1-3. Our experience with large intercalary allograft reconstruction has demonstrated high rates of long-term success and addresses the most common causes of large allograft failure (infection, fracture, and nonunion)4, as shown in our long-term outcome study1. Description: Once the tumor is resected, it is used as a template for cutting and shaping the allograft to fit the bone defect and to restore length and anatomy. The frozen allograft is thawed in a container with povidone iodine and bacitracin saline solution until it reaches room temperature. The allograft is size-matched, and clearance of its intramedullary marrow contents is performed with use of curets and intramedullary reamers7. If 1 end of the allograft includes the metaphysis and is covered by dense cancellous bone, we try not to ream through this end because maintaining this metaphyseal cancellous surface will expedite bone healing. The segment is then thoroughly lavaged with "triple wash" solutions to clear out any remaining marrow contents and to ensure sterilization of the allograft. This serial-wash technique involves the use of 3 discrete antiseptic modalities and has been utilized at our institution with low rates of allograft infection. These antiseptic modalities include 10% weight-per-volume povidone iodine diluted 1:1 with normal saline solution, 3% weight-per-volume hydrogen peroxide diluted 1:1 with normal saline solution, and 50,000 units of sterile bacitracin lyophilized powder dissolved in 500 mL of normal saline solution. Following the triple wash, the medullary canal is filled with antibiotic-laden methylmethacrylate bone cement. If both ends are open, the far end of the segment is first plugged with the surgeon's finger or with gauze, or if 1 end is covered with cancellous bone, then retrograde filling of the canal with cement is performed from the open end. The cement is then pressurized to ensure complete filling of the intramedullary space. Before it sets, 1 cm of cement is removed from each open end of the allograft to allow for packing of autograft bone cancellous chips and to ensure that cement does not impede anatomic reduction of the allograft-host bone junction. For this step, cancellous autograft from the iliac crest is harvested with use of a separate sterile surgical setup in order to prevent contamination of the autograft site by instruments used for tumor resection. The cancellous autograft is packed into the space created after recessing the cement at the end(s) of the allograft and, using a bone tamp, the autograft is compressed into this cavity and into the corresponding end of the host long bone in order to improve the healing potential at the allograft-host bone junction(s)8. Finally, a dual compression plate construct is utilized for upper as well as lower-extremity reconstructions in most cases. The cement in the allograft must be completely hardened before drilling into it. The allograft-host bone junctions are sequentially compressed at both the proximal and distal ends to allow for maximal apposition of the osseous surfaces. Only 1 or 2 unicortical screws are placed into the allograft to hold it in place and to facilitate maximal compression at both bone junctions. Patient compliance during postoperative rehabilitation is essential to optimize healing and provide reliable and durable outcomes. Postoperative care following the RAPTORS technique includes limited early rehabilitation and long periods of non-weight-bearing until radiographic union is noted across both bone junctions, followed by gradual resumption of weight-bearing and more aggressive physiotherapy. See the Appendix for further details regarding each step of the procedure. Alternatives: Intercalary reconstruction alternatives include various biological or endoprosthetic constructs. The other biological reconstruction options include the use of a free vascularized bone graft, distraction osteogenesis, combined vascularized fibula and allograft (i.e., the Capanna technique), or recycled tumor bones. Intercalary prostheses offer another reconstruction option for diaphyseal defects, but their feasibility is more limited in cases of periarticular segments with very short residual medullary canals. In such cases, there may be inadequate stem length for fixation, or the segment may require a custom implant that takes time to design and manufacture, which can be associated with high costs5. Rationale: Major factors limiting the widespread use of allografts include infection, graft fracture, graft nonunion, and, in some locations, availability4,6. Our technique of allograft preparation with dual compression plating and triple-washing to provide mechanical and antimicrobial protection as well as augmented healing has shown reproducible results with low complication rates compared with the literature. Expected Outcomes: There have been high rates of long-term allograft survival (84.4%) following intercalary long-bone reconstruction at our institution, with lower complication rates than those presented in the literature. Important Tips: Transverse osteotomies of the allograft, made perpendicular to the long axis of the diaphysis/anatomical axis, are important to replicate the resected host bone. Transverse osteotomies, while inherently less stable than step-cut ones, allow for adjusting the rotation of the allograft segment as needed for maximal contact and compression, as well as restoration of anatomical limb rotation.It is important to perform meticulous clearance of the intramedullary contents while preserving the endosteal bone and allograft integrity. We would utilize hand-reaming rather than a power drill device, in order to prevent overreaming or breaking through the allograft bone.Place as few unicortical screws as possible into the allograft-cement construct in order to maintain its structural strength and minimize potential sites for vascular ingrowth and bone resorption. Acronyms & Abbreviations: K-wires = Kirschner wiresW/V = weight per volume.

Surgical Outcomes of Primary Dermatofibrosarcoma Protuberans: A Retrospective, Multicenter Study.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a locally aggressive tumor with a low rate of metastatic disease. Previous series have shown a superiority of Mohs micrographic surgery (MMS) compared with wide local excision (WLE). Likewise, there is paucity of data examining the long-term follow-up of patients. OBJECTIVE: The purpose of the current study was to examine the outcome of surgical treatment of primary DFSP of the trunk and extremities. METHODS: We reviewed 236 patients (115 females, 121 males, mean age 41 ± 15 years) undergoing MMS (n = 81, 34%) or WLE (n = 155, 66%) to treat a primary DFSP. Mean tumor size and follow-up was 4 ± 2 cm and 7 years, respectively. Final margins were negative in 230 (97%) patients. RESULTS: There was no difference (p > 0.05) in patient age, sex, tumor size, negative margin excision, or history of a previous inadvertent excision between patients who underwent WLE and those undergoing MMS. There were two cases of local recurrence and two cases of metastasis, with no difference in the 5-year local recurrence-free survival (98% vs. 99%, p = 0.69) or metastatic-free survival (98% vs. 100%, p= 0.27) between WLE and MMS. CONCLUSION: There was no difference in oncologic outcome comparing MMS with WLE for DFSP outside the head and neck. The goal of treatment for DFSP is to achieve a negative margin, regardless of surgical treatment modalities. A 'less is more' approach to follow-up can likely be taken for patients with completely resected DFSP in easy-to-examine anatomical areas. In these patients, no formal follow-up should be required.

How Do the Outcomes of Radiation-Associated Pelvic and Sacral Bone Sarcomas Compare to Primary Osteosarcomas following Surgical Resection?

Radiation-associated sarcoma of the pelvis and/or sacrum (RASB) is a rare but challenging disease process associated with a poor prognosis. We hypothesized that patients with RASB would have worse surgical and oncologic outcomes than patients diagnosed with primary pelvic or sacral bone sarcomas. This was a retrospective, multi-institution, comparative analysis. We reviewed surgically treated patients from multiple tertiary care centers who were diagnosed with a localized RASB. We also identified a comparison group including all patients diagnosed with a primary localized pelvic or sacral osteosarcoma/spindle cell sarcoma of bone (POPS). There were 35 patients with localized RASB and 73 patients with POPS treated with surgical resection. Patients with RASB were older than those with POPS (57 years vs. 38 years, p < 0.001). Patients with RASB were less likely to receive chemotherapy (71% for RASB vs. 90% for POPS, p = 0.01). Seventeen percent of patients with RASB died in the perioperative period (within 90 days of surgery) as compared to 4% with POPS (p = 0.03). Five-year disease-specific survival (DSS) (31% vs. 54% p = 0.02) was worse for patients with RASB vs. POPS. There was no difference in 5-year local recurrence free survival (LRFS) or metastasis free survival (MFS). RASB and POPS present challenging disease processes with poor oncologic outcomes. Rates of perioperative mortality and 5-year DSS are worse for RASB when compared to POPS.

Automatic Registration and Error Color Maps to Improve Accuracy for Navigated Bone Tumor Surgery Using Intraoperative Cone-Beam CT.

Computer-assisted surgery (CAS) can improve surgical precision in orthopaedic oncology. Accurate alignment of the patient's imaging coordinates with the anatomy, known as registration, is one of the most challenging aspects of CAS and can be associated with substantial error. Using intraoperative, on-the-table, cone-beam computed tomography (CBCT), we performed a pilot clinical study to validate a method for automatic intraoperative registration. Methods: Patients who were ≥18 years of age, had benign bone tumors, and underwent resection were prospectively enrolled. In addition to inserting a navigation tracking tool into the exposed bone adjacent to the surgical field, 2 custom plastic ULTEM tracking tools (UTTs) were attached to each patient's skin adjacent to the tumor using an adhesive. These were automatically localized within the 3-dimensional CBCT volume to be used as image landmarks for registration, and the corresponding tracker landmarks were captured using an infrared camera. The main outcomes were the fiducial registration error (FRE) and the target registration error (TRE). The navigation time was recorded. Results: Thirteen patients with benign tumors in the femur (n = 10), tibia (n = 2), and humerus (n = 1) underwent navigation-assisted resections. The mean values were 0.67 ± 0.15 mm (range, 0.47 to 0.97 mm) for FRE and 0.83 ± 0.51 mm (range, 0.42 to 2.28 mm) for TRE. Registration was successful in all cases. The mean time for CBCT imaging and tracker registration was 7.5 minutes. Conclusions: We present a novel automatic registration method for CAS exploiting intraoperative CBCT capabilities, which provided improved accuracy and reduced operative times compared with more traditional methods. Clinical Relevance: This proof-of-principle study validated a novel process for automatic registration to improve the accuracy of resecting bone tumors using a surgical navigation system.

Investigating the Potential of Isolating and Expanding Tumour-Infiltrating Lymphocytes from Adult Sarcoma.

Sarcomas are a heterogeneous group of mesenchymal neoplasms, many of which are associated with a high risk of metastasis and poor prognosis. Conventional chemotherapy and targeted therapies have varying effects across individuals and tumour subtypes. The current therapies frequently provide limited clinical benefit; hence, more effective treatments are urgently needed. Recent advances in immunotherapy, such as checkpoint inhibition or adoptive cell therapy (ACT), show potential in increasing efficacy by providing a more personalized treatment. Therapy with tumour-infiltrating lymphocytes (TILs) is an emerging field in immunotherapy. Here, we collected 190 sarcoma tumour specimens from patients without pre-operative adjuvant treatment in order to isolate TILs. We compared different methods of TIL expansion and optimized a protocol specifically for efficacy in culturing TILs from sarcoma. The expanded TIL populations were characterized by flow cytometry analysis using CD3, CD4, CD8, CD14, CD19 and CD56 markers. The TIL populations were non-specifically stimulated to establish TIL reactivity. Through an optimized expansion protocol, TILs were isolated and cultured from 54 of 92 primary sarcoma specimens. The isolated TILs varied in CD4+ and CD8+ T-cell compositions and retained their ability to release IFNγ upon stimulation. Our results suggest that certain sarcoma subtypes have the potential to yield a sufficient number of TILs for TIL therapy.

Comparison of Prophylactic Intravenous Antibiotic Regimens After Endoprosthetic Reconstruction for Lower Extremity Bone Tumors: A Randomized Clinical Trial.

IMPORTANCE: The use of perioperative, prophylactic, intravenous antibiotics is standard practice to reduce the risk of surgical site infection after oncologic resection and complex endoprosthetic reconstruction for lower extremity bone tumors. However, evidence guiding the duration of prophylactic treatment remains limited. OBJECTIVE: To assess the effect of a 5-day regimen of postoperative, prophylactic, intravenous antibiotics compared with a 1-day regimen on the rate of surgical site infections within 1 year after surgery. DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical superiority trial was performed at 48 clinical sites in 12 countries from January 1, 2013, to October 29, 2019. The trial included patients with a primary bone tumor or a soft tissue sarcoma that had invaded the femur or tibia or oligometastatic bone disease of the femur or tibia with expected survival of at least 1 year who required surgical management by excision and endoprosthetic reconstruction. A total of 611 patients were enrolled, and 7 were excluded for ineligibility. INTERVENTIONS: A 1- or 5-day regimen of postoperative prophylactic intravenous cephalosporin (cefazolin or cefuroxime) that began within 8 hours after skin closure and was administered every 8 hours thereafter. Those randomized to the 1-day regimen received identical saline doses every 8 hours for the remaining 4 days; patients, care providers, and outcomes assessors were blinded to treatment regimen. MAIN OUTCOMES AND MEASURES: The primary outcome in this superiority trial was a surgical site infection (superficial incisional, deep incisional, or organ space) classified according to the criteria established by the Centers for Disease Control and Prevention within 1 year after surgery. Secondary outcomes included antibiotic-related complications, unplanned additional operations, oncologic and functional outcomes, and mortality. RESULTS: Of the 604 patients included in the final analysis (mean [SD] age, 41.2 [21.9] years; 361 [59.8%] male; 114 [18.9%] Asian, 43 [7.1%] Black, 34 [5.6%] Hispanic, 15 [2.5%] Indigenous, 384 [63.8%] White, and 12 [2.0%] other), 293 were randomized to a 5-day regimen and 311 to a 1-day regimen. A surgical site infection occurred in 44 patients (15.0%) allocated to the 5-day regimen and in 52 patients (16.7%) allocated to the 1-day regimen (hazard ratio, 0.93; 95% CI, 0.62-1.40; P = .73). Antibiotic-related complications occurred in 15 patients (5.1%) in the 5-day regimen and in 5 patients (1.6%) allocated to the 1-day regimen (hazard ratio, 3.24; 95% CI, 1.17-8.98; P = .02). Other secondary outcomes did not differ significantly between treatment groups. CONCLUSIONS AND RELEVANCE: This randomized clinical trial did not confirm the superiority of a 5-day regimen of postoperative intravenous antibiotics over a 1-day regimen in preventing surgical site infections after surgery for lower extremity bone tumors that required an endoprosthesis. The 5-day regimen group had significantly more antibiotic-related complications. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01479283.