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Background: We reviewed cases of soft-tissue sarcoma of the foot to gain insight into the presentation, treatments and outcomes for this rare disease and to determine whether limb-salvage surgery yields reasonable functional and oncological outcomes.Methods: We reviewed the cases of 16 patients treated by 2 of us (R.T. and M.I.) for soft-tissue sarcoma of the foot over a 15-year period. We extracted the following information from each patient's medical record: disease status at presentation, prior treatment, histological diagnosis, American Joint Committee on Cancer (AJCC) stage, details of treatment, oncological outcome and functional outcome. Functional outcome was assessed with the Toronto Extremity Salvage Score (TESS) and the Musculoskeletal Tumor Society (MSTS 1987).Results: Follow-up averaged 6 (range 2–15) years. Eight patients presented after unplanned excision. Histological diagnosis was synovial sarcoma for 7 of 16 patients.The tumours were evenly distributed among the hindfoot, midfoot and forefoot. Most patients (n = 13) presented with AJCC stage II or III disease. Amputation was necessary for 3 patients, whereas limb salvage was possible for the other 13. Free tissue transfer (n = 9) and radiation therapy (n = 12) were used in most cases. Surgical margins were microscopically positive in 4 of the 13 patients treated with limb salvage.Local disease recurred in 2 patients. Lung metastases occurred in 4 patients. At last follow-up, 11 of 16 patients were alive without disease, 2 with disease and 3 had died of their disease. Functional assessment with MSTS 1987 and the TESS averaged 28%and 90%, respectively, after limb salvage.Conclusion: In this series, we found that, first, patients frequently presented after unplanned excision, and this may have led to worse oncological outcomes compared with patients who presented primarily. Second, limb salvage was usually possible, but it required accepting marginal resections, relying on free tissue transfer to obtain coverage and using radiation therapy to obtain local control. Third, this combination yielded an acceptable local control rate and very good functional outcomes. [ABSTRACT FROM AUTHOR]

Background: Soft-tissue sarcoma involving the popliteal fossa remains challenging because it is difficult to achieve wide margins with limb salvage in this location. Adjuvant therapy is frequently necessary, and limb function can be adversely affected. We reviewed our experience with these tumours.Methods: Our prospective tumour database served to identify all patients with popliteal sarcomas treated at the McGill University Health Centre and the Maisonneuve-Rosemont Hospital between 1994 and 2005. We assessed oncologic and functional outcomes as well as complications.Results: Our study included 18 patients (12 women and 6 men). The mean age was 54 (range 16-84) years. The mean duration of follow-up was 55 (range 4-126) months. Frequent histologic diagnoses were liposarcoma (n = 6), synovial sarcoma (n = 4) and leiomyosarcoma (n = 3). Tumour size varied from 2 to 21 cm (median 11 cm). American Joint Committee on Cancer staging was as follows: 4 patients had stage IIa disease, 3 patients had stage IIb, 10 patients had stage III and 1 patient had stage IV disease. Treatment consisted of limb salvage in 15 patients and amputation in 3. Fourteen patients had radiotherapy, 4 had chemotherapy, and 3 needed partial sciatic nerve resection. Margins were negative in 7 of 18 patients and microscopically positive in 11 patients. Complications included wound infections in 3 patients and thrombophlebitis in 2 patients. Of the patients undergoing limb-salvaging procedures, 1 experienced local recurrences after limb salvage (7%), and 5 experienced lung metastases (20%). Local recurrence was always associated with positive margins, whereas metastases occurred only in patients without local recurrence. The mean Musculoskeletal Tumor Society 1987 score was 33 (range 24-35). The mean Toronto Extremity Salvage Score results was 82.4 (range 63.8-100). At latest follow-up, 6 patients had died of disease, 1 was alive with disease, and 11 (61%) patients remained free of disease.Conclusion: Despite the high rate of microscopically positive margins, the local recurrence rate was 7%. Amputation did not prevent death. We found function to be good to excellent in most patients who had limb-salvaging surgery. [ABSTRACT FROM AUTHOR]

Published reports dealing with tumor prosthesis have yet to establish a clear advantage of using either cemented or cementless implants. We examined the outcome and complications with modular cemented implants in 135 patients identified from our database to strengthen the argument for routine use of cemented constructs. The minimum followup was 1.4 months (mean, 57 months; median, 47 months; range, 1.4-157 months). The majority of patients (104) had sarcoma. The complications included: 11 infections, three of which underwent amputation and one a stem revision; eight local recurrences, five of which underwent amputation; three hip dislocations; and three incidents of shoulder instability. One periprosthetic femur fracture was stabilized operatively. There was no aseptic loosening or stem fracture. The 5-year survival rates for distal femoral and proximal humeral replacements were 84% and 70%; the 10-year survival rates were 79% and 59%. The 5-year survival rates for proximal femur and proximal tibia replacements were 78% and 37%. Average Musculoskeletal Tumor Society 1987 scores and Toronto Extremity Salvage Scores were 21.5 and 73% for proximal femur, 28.1 and 67% for distal femur, and 21 and 78% for proximal humerus. The survival of the endoprostheses related to site of bone resection. Cemented constructs of modern design in the context of tumor surgery provide good short-term results. [ABSTRACT FROM AUTHOR]

Objective: To assess the clinical impact of regular whole-body magnetic resonance imaging (WBMRI) surveillance in myxoid liposarcoma patients., Methods: This was a retrospective cohort study of myxoid liposarcoma patients who underwent at least one WBMRI at our institution between October 2006 and December 2020. The effect of WBMRI on clinical management, namely treatment modification or additional diagnostic investigations was studied. A standardised WBMRI surveillance protocol was instituted in 2015. We compared patient outcomes for the metastatic patients who had and had not received regular WBMRI surveillance and performed survival analysis for both subgroups., Results: Of the 56 patients (60.7% male, median age: 48.1 years) who underwent 345 WBMRI, 17 (30.3%) had metastases, and 168 WBMRI were performed in this group. The median imaging follow-up for the entire cohort was 35 months; the metastatic group had a median follow-up of 42 months. WBMRI changed the clinical management in 13 (76.5%) metastatic patients, with 33 instances of treatment modification. Thirty-five lesions were labelled 'indeterminate,' 16 (45.7%) had additional investigations/interventions, and 4 (11.4%) were confirmed to be metastatic. Twenty-one metastatic lesions were missed initially on WBMRI and confirmed on subsequent WBMRI, of which 5 (23.8%) were clinically significant. The 5-year survival since the detection of metastasis was better in the regular surveillance subgroup (85.7% vs. 45%), but this was not statistically significant (p = 0.068). Five patients (8.9%) developed their first metastasis more than 5 years after diagnosing the primary lesion., Conclusion: Regular WBMRI surveillance of myxoid liposarcoma patients considerably impacts clinical management by frequently influencing treatment decisions., Clinical Relevance Statement: WBMRI has been recently recommended as an imaging option for the staging and surveillance of myxoid liposarcoma patients. Our study highlights the impact of regular WBMRI surveillance on the clinical management of these patients and how it affects their survival., (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

Background: Advancements in musculoskeletal oncologic treatment have allowed for longer survival of patients with malignant bone tumors and the associated longer use of tumor endoprostheses in those who have had such reconstructions. Several studies have reported on increased serum metal ions with the use of such implants. Modularity in these implants introduces the risk of taper junction corrosion and subsidence resulting in metal wear particle release that may cause an adverse local tissue reaction or systemic toxicity. Additionally, these implants contain a large surface area of cobalt and chromium. It is unclear whether the source of the increased serum ion levels was due to the taper junction corrosion or the implant itself. To our knowledge, no prior study has reported on taper junction subsidence., Questions/purposes: In this study we sought (1) to determine survivorship free from radiographic taper junction subsidence in a femoral modular tumor endoprosthesis, and (2) to identify the implant characteristics in the endoprostheses associated with taper subsidence., Methods: Between January 1996 and February 2020, the senior author performed 150 proximal or distal femur replacements following resections of soft tissue or bone tumors of the thigh and femur. Of those, 6% (9 of 150) of patients were lost to follow-up before 2 years, 25% (37 of 150) could not be analyzed due to absence of plain radiographs during follow-up, and 13% (20 of 150) died before 2 years follow-up, leaving 56% (84 of 150) for analysis in this retrospective study, with a median time for analysis of 14 years (range 2 to 31 years) after the index resection and endoprosthetic reconstruction for patients with distal femur replacements and 5 years (range 2 to 19 years) for patients with proximal femur replacement. Radiographs involving the entire implant were evaluated for the presence or absence of subsidence of the taper junction that was evident and clear to see if present. The association between the number of taper junctions, the length of resection, the number of collapsed junctions, and the time to collapse from the initial surgery were examined using regression analysis., Results: Overall, 14% (12 of 84) patients with a distal femur replacement had radiographic collapse of at least one of the modular tapers. Survivorship free from taper subsidence was 91% (95% CI 86% to 96%) at 10 years and 84% (95% CI 78% to 90%) at 20 years. All patients were in the distal femur replacement group. The median follow-up of patients with subsidence was 15 years (range 5 to 26). Fifty-eight percent (7 of 12) of patients had two junctions involved, 25% (3 of 12) had three junctions, and 17% (2 of 12) had one junction involved. All but one patient had subsidence in a single junction. The median time to subsidence was 15 years (range 4.5 to 24.0 years). The subsidence was progressive in all patients who demonstrated it. The taper junction subsidence was complete in 75% (9 of 12) of patients and partial in 25% (3 of 12). Univariate and multivariable regression analyses did not show that the risk factors we studied were associated with subsidence. Two patients with junction subsidence were revised, one for taper fracture and one during busing exchange for distal junction subsidence., Conclusion: Taper damage with late and progressive subsidence of the intervening junction is not uncommon after distal femur replacement. The impact of such a complication is still unknown. Further studies should examine the long-term outcomes and correlate them with metal ion levels., Level of Evidence: Level III, therapeutic study., Competing Interests: Each author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request., (Copyright © 2024 by the Association of Bone and Joint Surgeons.)

Purpose: We aimed to describe the level of agreement between patients and physicians on the ratings of daily functioning and pain in a cohort of sarcoma patients and assess how (dis)agreement and its change over time predicted patient-reported outcomes in survivorship., Method: We performed secondary analysis of longitudinal data from a sarcoma-specialty clinic in Montreal, Canada. Demographics, clinical characteristics and patient-physician agreement were summarized descriptively. Linear mixed models were used to assess the effects of time, baseline agreement, change in agreement over time, interaction of time and change in agreement and 12-month daily functioning, quality of life, and fatigue., Results: Data were available for 806 patients (57.7% male, x̄ = 53.3 years) who completed at least one questionnaire. Patient-physician disagreement was common on the level of function (43.4%) and pain (45.7%). Baseline physician-patient agreement was associated with better 12-month outcomes. Improvement in agreement on function over time was significantly associated with daily functioning (F(2, 212) = 3.18, p = 0.043) and quality of life (F(2, 212) = 3.17, p < 0.044). The pattern was similar though less pronounced for the agreement on pain., Conclusions: Our study offers novel insights into the importance of patient-physician agreement and communication's role in long-term patient-reported outcomes in sarcoma., Implications for Cancer Survivors: The results emphasize the importance of mutual understanding of symptoms and patients' needs and suggest that further consultation in cases of discordance of ratings and opinions might be beneficial for optimal survivorship., (© 2023. The Author(s).)

Study Design: A systematic review of the literature and pooled data analysis of treatment outcomes of primary sarcomas of the spine., Objective: To examine the current literature and treatment options for primary sarcomas of the spine., Summary of Background Data: A paucity of literature exists on treatment outcomes of primary sarcomas of the spine., Materials and Methods: Two authors searched PubMed to identify articles for review, and a pooled data analysis was performed to determine overall survival for each type of surgical resection on spine sarcomas., Results: In total, 1776 articles were identified, and 11 met our inclusion criteria for review. In chondrosarcoma, overall survival was significantly higher with en bloc excision when compared with piecemeal resection (HR for piecemeal resection: 4.11; 95% CI: 2.08-8.15). Subgroup analysis showed that the addition of radiation therapy after piecemeal excision increased overall survival to 60 months from 48 months with piecemeal excision alone. In osteosarcoma, there was no significant difference in overall survival between en bloc and piecemeal resection (HR for piecemeal resection: 1.76; 95% CI: 0.776-3.99). In Ewing's sarcoma, overall survival was significantly higher when a successful en bloc resection was achieved and coupled with chemotherapy and radiation therapy for local control (HR for piecemeal resection: 7.96; 95% CI: 2.12-20.1). Interestingly, when a successful en bloc resection could not be achieved, chemotherapy and radiation therapy alone had significantly higher survival than piecemeal resection (HR for piecemeal resection: 2.63; 95% CI: 1.01-6.84). A significantly higher number of local recurrences were associated with the piecemeal resection group in all types of spine sarcomas., Conclusion: This review and pooled data seem to favor en bloc excision for local control as the treatment of choice in primary sarcomas of the spine., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Orthopedic oncology surgeons commonly engage in prolonged and complex surgical procedures. These types of surgeries increase the risk of physical and psychological stressors, which may in turn make these physicians prone to work-related occupational injuries., Aim: The aim of this study was to explore in orthopedic oncologists, the prevalence of work-related physical injuries and psychological disturbances., Methods: A modified version of the physical discomfort survey was developed to assess occupational injuries among orthopedic oncology surgeon members of the Musculoskeletal Tumor Society, the Canadian Orthopedic Oncology Society and European Musculoskeletal Oncology Societies. The survey was sent by email, and it explored musculoskeletal complaints, psychological disturbances, treatment required for these complaints and the requirement of time off work., Results: A total of 67 surgeon responses were collected. A high number of orthopedic oncologists (84%) reported an occupational injury. Low back pain (39%) was the most prevalent musculoskeletal condition, followed by lumbar disk herniation (16%), shoulder tendinitis (15%) and lateral epicondylitis (13%). Of the cohort, 46% required surgery and 31% required time off work due to their injury. Thirty-three respondents reported a psychological disorder. Burnout (27%), anxiety (20%) and insomnia (20%) were the most commonly reported. Time required off work due to injury was associated with old age and years in practice., Conclusion: Orthopedic oncology surgeons report a high prevalence of work-related disorders. Lower back related injury and burnout were the most reported disorders. Improving operative room ergonomics and prevention of stress related to the work environment should be areas to explore in upcoming research., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Periprosthetic joint infections (PJI) are catastrophic complications for patients with implanted megaprostheses and pose significant challenges in the management of orthopaedic oncology patients. Despite various preventative strategies, with the increasing rate of implanted orthopaedic prostheses, the number of PJIs may be increasing. PJIs are associated with a high rate of amputation. Therefore, novel strategies to combat bacterial colonization and biofilm formation are required. A promising strategy is the utilization of anti-bacterial coatings on megaprosthetic implants. In this translational review, a brief overview of the mechanism of bacterial colonization of implants and biofilm formation will be provided, followed by a discussion and classification of major anti-bacterial coatings currently in use and development. In addition, current in vitro outcomes, clinical significance, economic importance, evolutionary perspectives, and future directions of anti-bacterial coatings will also be discussed. Megaprosthetic anti-bacterial coating strategies will help reduce infection rates following the implantation of megaprostheses and would positively impact sarcoma care. STATEMENT OF SIGNIFICANCE: This review highlights the clinical challenges and a multitude of potential solutions to combating peri-prosthetic join infections in megaprotheses using anti-bacterial coatings. Reducing infection rates following the implantation of megaprostheses would have a major impact on sarcoma care and major trauma surgeries that require reconstruction of large skeletal defects., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Solitary fibrous tumor (SFT) is a rare mesenchymal tumor with an intermediate tendency to metastasize. Meningeal hemangiopericytoma (HPC), arising in the meningeal membranes, also is considered an SFT. Although SFT is assumed to show an unpredictable behavior, the authors defined some factors associated with its aggressive behavior., Methods: This retrospective study was based on the medical records of 81 SFT patients treated surgically, with the median follow-up period of 59 months. The patients were assigned to three histopathologic groups based on the 2016 WHO classification: group 1 (SFT, 29 patients), group 2 (cellular SFT/hemangiopericytoma [HPC], 27 patients), and group 3 (malignant SFT/anaplastic HPC, 25 patients)., Results: The SFT histopathologic classification was associated with distant metastasis (DM) (p = 0.007). The multivariate analysis showed that cellular SFT had an independent impact on DM (odds ratio [OR] = 25.42; p = 0.006). Tumor diameter larger than 7.25 cm was correlated with DM (p = 0.010) and the patient's disease-specific death (DSD) (p = 0.007). A 1-cm increase in tumor diameter enhanced the likelihood of metastasis by 1.26 (OR = 1.26; 95% confidence interval [CI], 1.05-1.53). Tumors originating from the central nervous system (CNS) showed a greater tendency toward local recurrence (LR) (p = 0.039) and DM (p = 0.05). Radiotherapy had no association with LR, DM, or DSD. The 10-year disease-specific survival rate was 82.7%., Conclusions: Tumor size and histopathologic diagnosis are the predictors of SFT's aggressive behavior. Cellular SFTs behave as aggressively as the malignant form of the tumor. A SFT grading based on SFT cellularity would contribute to anticipation of its aggressive behavior., (© 2021. Society of Surgical Oncology.)

Background: Both cemented and cementless stemmed endoprosthetic implants have been used to reconstruct large skeletal defects after tumor resection with similar outcomes. In this study, we examined the oncologic, clinical, and functional outcomes in patients undergoing distal femur replacement using the French paradox technique., Methods: A total of 125 patients who underwent distal femur replacement between 1990 and 2019 using the line-to-line cementation technique were reviewed. Implant failure was recorded as per Henderson's classification. Functional outcomes were analyzed using the Musculoskeletal Tumor Society and Toronto Extremity Salvage Score scoring systems. The mean follow-up was 84 (1-350) months., Results: Aseptic loosening of the femoral stem was recorded in one patient at 21-years of follow-up. Twenty of 125 patients required bushing exchange for polyethylene wear, all after 10 years. Six tibial bearing component fractures were recorded in four patients while one femoral stem component Morse taper fractured. Two all-polyethylene cemented tibial implants were revised for polyethylene granuloma. Deep surgical site infection occurred in 13 patients, while six patients experienced local recurrence. Kaplan-Meier estimates for implant survival for all-cause revision were 85% at 1 year and 70% at 5 years. These estimates for femur or tibia loosening as an end point were 96% at 10 years and 90% at 15 years. The mean Musculoskeletal Tumor Society and Toronto Extremity Salvage Score scores at the last follow-up were 76% and 74%, respectively. Thirty-five patients died of disease progression., Conclusion: The line-to-line cementation technique, used with all-polyethylene tibial implants, demonstrates low incidence of aseptic loosening at medium and long-term follow-ups., Level of Evidence: III., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Intra- and juxta-articular osteoid osteoma (OO) is rare and can result in irreversible joint damage. Recently, arthroscopic surgery is being used more and more to avoid complications associated with other treatment modalities., Methods: On October 13, 2019, we conducted a systematic review of the literature available in PubMed and EMBASE regarding the arthroscopic management of OO involving the joints of the upper extremity. Predetermined inclusion criteria were used to include any relevant article published on and before that date for further analysis. Treatment success rate and tumor recurrence rate were considered the primary outcomes in our analysis., Results: Out of 113 studies, 19 met our inclusion criteria. Of the 32 reported cases in these 19 articles, ten involved the shoulder joint, 19 involved the elbow joint and three involved the wrist joint. Overall treatment success rate was 93.8%. Tumor recurrence rate was 0.0%. No postoperative complications (0.0%) were reported among cases involving the shoulder joint. Two out of 24 (8.3%) patients with elbow OO failed arthroscopic treatment due to incomplete excision, and two (4%) experienced minor complications. Among the three cases of wrist OO, two (66.7%) patients had residual postoperative pain and decreased hand grip strength., Conclusion: Arthroscopic management of OO of the upper extremity joints is highly successful and results in no tumor recurrence; however, there is a risk of incomplete resection in areas more difficult to access by arthroscopy.

Background: Endoprostheses are frequently used in the management of tumors involving the proximal femur. Aseptic loosening is a common complication that has been linked to the cementing technique. The "French paradox" is well-known cementing technique in the arthroplasty literature. No previous reports have assessed loosening in proximal femur replacements using this technique. We examined rates of femoral stem aseptic loosening in proximal femur replacements, functional outcomes, complications, and oncologic outcomes., Methods: We conducted a retrospective review of 47 patients who underwent proximal femur replacement between 2000 and 2019. Two reviewers evaluated preoperative and postoperative radiographs using the International Society of Limb Salvage scoring system and Barrack criteria for stem loosening. The acetabulum was evaluated according to the criteria of Baker et al. Functional outcomes were assessed using Musculoskeletal Tumor Society (MSTS) score and Toronto Extremity Salvage Score. The mean follow-up was 44 months., Results: The mean International Society of Limb Salvage scores for the 2 reviewers were 86% ± 6% and 84% ± 6%. The first reviewer graded femoral stem loosening as "possibly loose" in 2 patients, one of whom was graded as possibly loose by the second reviewer. The 2 reviewers found no acetabular erosion in 16 (70%) and 15 (65.4%) patients, respectively. The mean Musculoskeletal Tumor Society score and Toronto Extremity Salvage Score at last follow-up were 61% and 72%, respectively. Twenty complications occurred in 13 patients, and 5 patients experienced local recurrence., Conclusion: Despite complications, we showed favorable femoral component survival rates. Cementing the proximal femur prosthesis with tight canal fit and thin cement mantle is a viable option for the short and medium term., Level of Evidence: III., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background and Objectives: This study explored psychological functioning and coping styles in adult patients with soft-tissue sarcoma who underwent surgical procedures in a single expert sarcoma medical center in Canada., Methods: This is a qualitative study with three formats of data collection. The interview guide was based on theoretical health-related quality of life model. We began the investigation with 2 online and 2 in-person focus groups. Four individual semistructured interviews were added to further explore emerging themes. Data were analyzed using inductive thematic networks approach., Results: Twenty-eight adults (13 female, 24-75 years of age) participated. In the domain of psychological functioning we identified three main themes; changes in mood, worry, and body image concerns. In the domain of coping styles, we identified four adaptive coping styles; positive reframing and optimism, finding a purpose, being proactive, and using humor. Among the maladaptive coping styles, we found passive acceptance, and avoidance and denial., Conclusions: Psychological well-being can be contingent on physical functioning and coping styles in adults with soft-tissue sarcoma. Both psychological and physical function impact quality of life. Patients with more physical limitations, psychological distress and maladaptive coping styles should be monitored for their well-being., (© 2020 The Authors. Journal of Surgical Oncology published by Wiley Periodicals, Inc.)

Hemangioendotheliomas are a heterogeneous group of vascular neoplasm that may affect the liver, bone, and soft tissues. Among its variants, pseudomyogenic hemangioendothelioma is rarely encountered. Pseudomyogenic hemangioendothelioma is usually characterized by multiple soft tissue lesions, with occasional bone lesions. Fewer than 20 cases with exclusive involvement of bone structures have been reported. We describe a case of pseudomyogenic hemangioendothelioma involving multiple bony structures but without soft tissue involvement in a 7-year-old girl, imaged with F-FDG PET/CT at diagnosis and during treatment with mammalian target of rapamycin inhibitors.

Background: Distal radius giant cell tumour (GCT) is known to be associated with distinct management difficulties, including high rates of local recurrence and lung metastases compared to other anatomic locations. Multiple treatment options exist, each with different outcomes and complications., Questions/purposes: To compare oncological and functional outcomes and complications following treatment of patients with distal radius GCT by extended intralesional curettage (EIC) or resection-arthrodesis., Methods: Patients operated on for distal radius GCT were identified from prospectively collected databases at four Canadian musculoskeletal oncology specialty centres. There were 57 patients with a mean age of 35.4 years (range 17-57). Thirteen tumours were Campanacci grade 2, and 40 were Grade 3 (4 unknown). Twenty patients presented with an associated pathologic fracture. There were 34 patients treated by EIC and 23 by en bloc resection and wrist arthrodesis. All resections were performed for grade 3 tumours. The mean follow-up was 86 months (range 1-280)., Results: There were a total of 11 (19%) local recurrences: 10 of 34 (29%) in the EIC group compared to only 1 of 23 (4%) in the resection-arthrodesis group (p = 0.028). For the 10 patients with local recurrence following initial treatment by EIC, 7 underwent repeat EIC, while 3 required resection-arthrodesis. The one local recurrence following initial resection was managed with repeat resection-arthrodesis. Six of the 11 local recurrences followed treatment of Campanacci grade 3 tumours, while 4 were in grade 2 lesions and in one case of recurrence the grade was unknown. There were no post-operative complications after EIC, whereas 7 patients (30%) had post-operative complications following resection-arthrodesis including 4 infections, one malunion, one non-union and one fracture (p = 0.001). The mean post-operative Musculoskeletal Tumor Society score was 33.5 in the curettage group compared to 27 in the resection group (p = 0.001). The mean Toronto Extremity Salvage Score was 98.3% following curettage compared to 91.5% after resection (p = 0.006). No patients experienced lung metastasis or death., Conclusions: EIC is an effective alternative to wide resection-arthrodesis following treatment of distal radius GCT, with the advantage of preserving the distal radius and wrist joint function, but with a higher risk of local recurrence. Most local recurrences following initial treatment by EIC could be managed with iterative curettage and joint preservation. Wide excision and arthrodesis were associated with a significantly lower risk of tumour recurrence but was technically challenging and associated with more frequent post-operative complications. EIC was associated with better functional scores. Resection should be reserved for the most severe grade 3 tumours and recurrent and complex cases not amenable to treatment with EIC and joint salvage., Level of Evidence: III, retrospective comparative trial.

Background: The physical function of children with sarcoma after surgery has not been studied explicitly. This paucity of research is partly because of the lack of a sufficiently sensitive pediatric functional measure. The goal of this study was to establish and validate a standardized measure of physical function in pediatric patients with extremity tumors., Questions/purposes: (1) What is the best format and content for new upper- and lower-extremity measures of physical function in the pediatric population? (2) Do the new measures exhibit floor and/or ceiling effects, internal consistency, and test-retest reliability? (3) Are the new measures valid?, Methods: In Phase 1, interviews with 17 consecutive children and adolescents with bone tumors were conducted to modify the format and content of draft versions of the pediatric Toronto Extremity Salvage Score (pTESS). In Phase 2, the pTESS was formally translated into French. In Phase 3, 122 participants between 7 and 17.9 years old with malignant or benign-aggressive bone tumors completed the limb-specific measure on two occasions. Older adolescents also completed the adult TESS. Floor and ceiling effects, internal consistency, test-retest reliability, and validity were evaluated., Results: Feedback from interviews resulted in the removal, addition, and modification of draft items, and the pTESS-Leg and pTESS-Arm questionnaires were finalized. Both versions exhibited no floor or ceiling effects and high internal consistency (α > 0.92). The test-retest reliability was excellent for the pTESS-Leg (intraclass correlation coefficient [ICC] = 0.94; 95% CI, 0.90-0.97) and good for the pTESS-Arm (ICC = 0.86; 95% CI, 0.61-0.96). Known-group validity (ability to discriminate between groups) was demonstrated by lower mean pTESS-Leg scores for participants using gait aids or braces (mean = 68; SD = 21) than for those who did not (mean = 87; SD = 11; p < 0.001). There was no significant difference between pTESS arm scores among respondents using a brace (n = 5; mean = 73; SD = 11) and those without (n = 22; mean = 83; SD = 19; p = 0.13). To evaluate construct validity, we tested a priori hypotheses. The duration since chemotherapy correlated moderately with higher pTESS-Leg scores (r = 0.4; p < 0.001) but not with pTESS-Arm scores (r = 0.1; p = 0.80), and the duration since tumor resection correlated moderately with higher pTESS-Leg scores (r = 0.4; p < 0.001) but not pTESS-Arm scores (r = 0.2; p = 0.4). Higher VAS scores (that is, it was harder to do things) antecorrelated with both pTESS versions (pTESS-Leg: r = -0.7; p < 0.001; pTESS-Arm: r = -0.8; p < 0.001). To assess criterion validity, we compared the pTESS with the current "gold standard" (adult TESS). Among adolescents, strong correlations were observed between the TESS and pTESS-Leg (r = 0.97, p < 0.001) and pTESS-Arm (r = 0.9, p = 0.007)., Conclusions: Both pTESS versions exhibited no floor or ceiling effects and had high internal consistency. The pTESS-Leg demonstrated excellent reliability and validity, and the pTESS-Arm demonstrated good reliability and reasonable validity. The pTESS is recommended for cross-sectional evaluation of self-reported physical function in pediatric patients with bone tumors., Level of Evidence: Level II, outcome measurement development.

Osteoid osteomas (OOs) are rare benign bone tumors that may occur in various joints including the ankle. These tumors are generally removed via open surgical excision or radiofrequency ablation. However, when they occur intra-articularly, these treatments are more difficult to perform because of more difficult access and the increased risk of damaging articular cartilage. Therefore, some have advocated for the use of arthroscopy to treat these cases. This systematic review aims to investigate the safety and efficacy of arthroscopic treatment for intra-articular OO of the ankle. Using Medline and Embase, we systematically reviewed the literature as of May 31, 2017. All articles published on and before that date were reviewed by 2 independent reviewers. Seventeen articles containing a total of 27 cases were included in the review. Most reported cases were in the talar neck, followed by the distal tibia. Of all the cases, only 2 recurrences were reported (in the same patient), and no complications were reported. Therefore, these cases demonstrate arthroscopic excision of intra-articular OO of the ankle as a safe and effective alternative to open surgical excision and radiofrequency ablation, with a success rate of 96%. However, all articles found were case studies or small case series owing to the rarity of this disease. In the future, analyses of case series with larger case collections should be performed., (Copyright © 2018 the American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Developing multiple soft tissue sarcomas (STSs) is a rare process, sparsely reported in the literature to date. Little is known about the pattern of disease development or outcomes in these patients. Patients were identified from three tertiary orthopaedic oncology centres in Canada and the UK. Patients who developed multiple extremity STSs were collated retrospectively from prospective oncology databases. A literature review using MEDLINE was also performed. Six patients were identified in the case series from these three institutions, and five studies were identified from the literature review. Overall, 17 patients were identified with a median age of 51 years (range: 19 to 77). The prevalence of this manifestation in STS patients is 1 in 1225. The median disease-free interval between diagnoses was 2.3 years (range: 0 to 19 years). Most patients developed the secondary STS in a metachronous pattern, the remaining, synchronously. The median survival after the first sarcoma was 6 years, and it was 1.6 years after the second sarcoma. The 5-year overall survival rate was 83.3% and 50% following the first and second STS diagnoses, respectively. A diagnosis of two STSs does not confer a worse prognosis than the diagnosis of a single STS. Developing a second STS is a rare event with no identifiable histological pattern of occurrence. Presentation in a metachronous pattern is more common. A high degree of vigilance is required in patients with a previous STS both to detect both local recurrence and to identify new masses remote from the previous STS site. Acquiring an early histological diagnosis should be attempted.

Objective: To define the role of whole-body MRI (WBMRI) for initial staging and routine follow-up of myxoid liposarcoma (MLS)., Materials and Methods: A retrospective review of all the patients with MLS who underwent WBMRI for initial staging and routine follow-up at our institution between October 1, 2006, and September 30, 2016 was performed. Patient demographics, clinical presentation, imaging findings, tumor histology, and occurrence and location of metastatic disease were recorded. Thirty-three patients who underwent a total of 150 WBMRI examinations were included in the study., Results: Nine patients (27%) were diagnosed with metastases between 0 and 60 months (median 10; interquartile range, 7-13) from the diagnosis of the primary tumor. The initial site of metastatic disease was extrapulmonary in all patients. Only two patients developed pulmonary metastases, which were diagnosed by CT chest 9 and 29 months after the diagnosis of extrapulmonary metastases. The first metastasis was diagnosed by WBMRI in seven patients (78%), by thoracic CT in one patient, and by abdominal CT in one patient. Eight of nine patients (89%) were asymptomatic at the time of diagnosis of the metastases. In seven patients (78%), WBMRI demonstrated metastases included within the field of view of, but occult on a contemporaneous CT scan., Conclusion: Our 10-year institutional experience demonstrates that WBMRI facilitates early detection of extrapulmonary MLS metastases before the onset of clinical symptoms and pulmonary metastases. WBMRI also depicts extrapulmonary metastases that are occult on CT scans. The current surveillance strategies are insufficient for screening for extrapulmonary MLS metastases.

Background: Distal femoral endoprosthesis (DFE) has become the optimal method of reconstruction in the skeletally mature patients treated for malignant bone tumor. Albeit literature has reported wide range of aseptic loosening in cemented components (6-32%), few authors showed that cement was not detrimental to long-term success of primary distal femoral implants possibly relating to cementing technique., Methods: A series of consecutive of DFE (MRS and GMRS, Styker Orthopaedics, Mahwah, NJ) was retrospectively reviewed for evidence of loosening on plain radiographs. All prostheses had the standard straight 127-mm stem and a cemented polyethylene tibial component. Cementing technique involved reaming line to line to the selected stem size and cementing without pressurization. Radiographs were assessed by two independent blinded reviewers and scored for radiolucent zones (>1 mm) and graded as not loose, possibly, probable and definite loose. Furthermore, the final reamer/stem diameters, length of resection, tumor type, adjuvant treatment modalities, bushing exchange/revision surgery and infection rate were recorded., Results: There were 70 patients and none were lost to follow-up. The average radiographic follow-up was 7.2 years (58% had f/u >5 years). Examiner A found 89% of femoral components to be "Not Loose" and 11% (n = 6) "Possibly Loose". Examiner B found 96% of femoral components to be "Not Loose" and 4% (n = 2) to be "Possibly Loose". No components scored as probably or definitely loose. Two DFE stems were reported as "Possibly Loose" by both reviewers. No femoral stem required revisions for either loosening, femur fracture or metal failure. Although infection was frequent, there was no septic loosening., Conclusion: Despite our study limitations, no radiographic evidence of loosening was found. Cementing distal femur prosthesis with a tight canal fit and with a thin and inconsistent cement mantle appears to be a viable option at short and medium term.

Several types of pediatric cancers reportedly contain high-frequency missense mutations in histone H3, yet the underlying oncogenic mechanism remains poorly characterized. Here we report that the H3 lysine 36-to-methionine (H3K36M) mutation impairs the differentiation of mesenchymal progenitor cells and generates undifferentiated sarcoma in vivo. H3K36M mutant nucleosomes inhibit the enzymatic activities of several H3K36 methyltransferases. Depleting H3K36 methyltransferases, or expressing an H3K36I mutant that similarly inhibits H3K36 methylation, is sufficient to phenocopy the H3K36M mutation. After the loss of H3K36 methylation, a genome-wide gain in H3K27 methylation leads to a redistribution of polycomb repressive complex 1 and de-repression of its target genes known to block mesenchymal differentiation. Our findings are mirrored in human undifferentiated sarcomas in which novel K36M/I mutations in H3.1 are identified., (Copyright © 2016, American Association for the Advancement of Science.)

Aim: To review outcomes following usage of the Ligament Advanced Reinforcement System (LARS(®)) in shoulder tumors., Methods: Medical records of nineteen patients (19 shoulders) that underwent tumor excisional procedure and reconstruction with the LARS synthetic fabric, were retrospectively reviewed., Results: Patients' median age was 58 years old, while the median length of resection was 110 mm (range 60-210 mm). Compared to immediate post-operative radiographs, the prosthesis mean end-point position migrated superiorly at a mean follow up period of 26 mo (P = 0.002). No statistical significant correlations between the prosthesis head size (P = 0.87); the implant stem body length (P = 0.949); and the length of resection (P = 0.125) with the position of the head, were found at last follow up. Two cases of radiological dislocation were noted but only one was clinically symptomatic. A minor superficial wound dehiscence, healed without surgery, occurred. There was no evidence of aseptic loosening either, and no prosthetic failure., Conclusion: LARS(®) use ensured stability of the shoulder following endoprosthetic reconstruction in most patients.

Background: Intra-articular osteoid osteoma (OO) causes irreversible joint damage. Its treatment of choice is radiofrequency ablation (RFA); however, some areas of the acetabulum are hard to access. Therefore, hip arthroscopy was used to treat this tumor. We aim to systematically review the literature with regards to arthroscopic management of acetabular OO, and to report a further case in which hip arthroscopy was used for treatment., Methods: PubMed and EMBASE were searched for articles relevant to the arthroscopic management of acetabular OO on December 2, 2014. All articles published on and before that date were reviewed, and studies which met our pre-determined inclusion criteria were included. Articles screening and data abstraction were done by two reviewers independently. We also presented a 31-year-old man with acetabular OO who underwent hip arthroscopy for the management of his tumor after failing to respond to medications and computed tomography scan (CT)-guided RFA., Results: The initial search revealed 14 studies, of which ten met our inclusion criteria. A total of ten patients underwent hip arthroscopy for the management of acetabular OO. Only two patients were females, and the patients' age ranged from 7 to 47 years. Two patients underwent arthroscopic guided-RFA of the lesion, while the rest underwent excision. The follow-up period ranged from 6 months to 2 years. Success rate was 100 %, and no recurrence was reported. Minor complications (transient impotence and perineal numbness) developed in one patient (10 %). Arthroscopic-guided RFA failed to eliminate the tumor in our additional case. A second trial of CT-guided RFA was successful in treating the patient's condition., Conclusions: Hip arthroscopy is an effective and safe option for the management of acetabular OO, with success rate exceeding 90 %. Studies of higher level of evidence are required.

Background: Complex anatomy of the forearm may impact on local control and survivals of soft tissue sarcoma. Little is known about characteristics and oncologic outcomes following surgical treatment., Methods: Demographic and tumor data of 117 patients with forearm soft tissue sarcoma were collected and analyzed. Following limb salvage, survivals, and prognostic factors were studied., Results: Seventy-three patients were males (62%) and 53 (45%) were referred after unplanned excision. Pleomorphic undifferentiated sarcoma was most frequent (45%). The average tumor size was 5.1 cm and grade III histology was mostly identified (53%). With radiotherapy, local recurrence occurs in 8 patients (7%) and 30 patients (24%) developed metastasis. Overall survival, disease free survival, local recurrence free survival, and metastasis free survival were 83%, 74%, 93%, and 74%, respectively. Better survival was found for grade I (80% vs. 60%) and small size (<5 cm) (72% vs. 47%). Large size tumor, extra-compartmental site, extramuscular, and virgin tumor were positive predictors of metastasis., Conclusion: Soft tissue sarcomas of the forearm are often referred after unplanned excision. Limb salvage was achieved for most and local recurrence remained low in context of radiotherapy. Metastatic progression remained frequent. Low grade and small size were predictors of survival., (© 2014 Wiley Periodicals, Inc.)

Current means of measuring RT-induced fibrosis are subjective. We evaluated the DermaLab suction cup system to measure objectively skin deflection as a surrogate for fibrosis. Sixty-nine patients with E-STS were treated with limb-sparing surgery and 50-66 Grays (Gy) of RT. Using a "scleroderma" DermaLab Suction Cup, the skin stiffness was measured by two clinicians. The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) scale, the Musculoskeletal Tumor Rating Scale (MSTS) and Toronto Extremity Salvage Score (TESS) questionnaires were completed for each patient. Levels of agreement between measurers were estimated using the Kappa (k) coefficient and the concordance correlation coefficient (CCC). All sixty-nine patients were included. The level of agreement between measurers for NCI-CTCAE grading was moderate (range k = 0.41-0.59). The CCC for the elasticity measurements were higher, with CCC = 0.82 for fibrotic skin and CCC 5 0.84 for normal skin. The elasticity measurements were significantly higher when MSTS scores were <30 and or TESS scores were <90. Suction Cup measurement of skin elasticity is more reproducible than CTCAE grading and shows promise in generating reproducible measurements for radiation-induced skin fibrosis. Furthermore, it correlates well with the MSTS and TESS.

Background: The distal tibia is an unusual location for a giant cell tumor (GCT). Treatment choices are unclear because of their rarity, the anatomy of the ankle, and difficulties associated with reconstruction., Questions/purposes: We assessed: (1) the treatment modalities used by participating Canadian bone tumor centers for distal tibia GCTs; (2) the incidence of local recurrence and their management; and (3) patients' function after treatment., Methods: A prospective tumor database served to identify all 31 patients with primarily treated distal tibia GCTs between 1991 and 2010. We extracted patients and tumor characteristics, treatment modalities for initial and recurrent tumors, and the Musculoskeletal Tumor Society (MSTS) and Toronto Extremity Salvage (TESS) scores. The median followup was 58 months (range, 24-192 months)., Results: Extended curettage was the only modality of treatment for all patients including all subsequent local recurrences. Nine had local recurrence, three of which had a second local recurrence; one had a third recurrence. Ultimately all patients were in remission at last followup. The local recurrence rate was 29% and appeared higher compared with recent series of all anatomic sites. The mean final MSTS and TESS scores were 91% (range, 71%-100%) and 88% (range, 35%-100%), respectively., Conclusions: Extended curettage was the unique modality of surgical treatment for all tumors. We found the incidence of local recurrence higher than that reported for other locations but recurrences were manageable with repeated curettage. Complications and function appeared better than those reported for series of ankle fusion or reconstruction for bone tumors.

Parathyroid-hormone-related protein (PTHrP) has been shown to be an important factor in osteolysis in the setting of metastatic carcinoma to the bone. However, PTHrP may also be central in the setting of primary bone tumors. Giant cell tumor of bone (GCT) is an aggressive osteolytic bone tumor characterized by osteoclast-like giant cells that are recruited by osteoblast-like stromal cells. The stromal cells of GCT are well established as the only neoplastic element of the tumor, and we have previously shown that PTHrP is highly expressed by these cells both in vitro and in vivo. We have also found that the stromal cells exposed to a monoclonal antibody to PTHrP exhibited rapid plate detachment and quickly died in vitro. Therefore, PTHrP may serve in an autocrine manner to increase cell proliferation and promote invasive properties in GCT. The purpose of this study was to use transcriptomic microarrays and functional assays to examine the effects of PTHrP neutralization on cell adhesion, migration and invasion. Microarray and proteomics data identified genes that were differentially expressed in GCT stromal cells under various PTHrP treatment conditions. Treatment of GCT stromal cells with anti-PTHrP antibodies showed a change in the expression of 13 genes from the integrin family relative to the IgG control. Neutralization of PTHrP reduced cell migration and invasion as evidenced by functional assays. Adhesion and anoikis assays demonstrated that although PTHrP neutralization inhibits cell adhesion properties, cell detachment related to PTHrP neutralization did not result in associated cell death, as expected in mesenchymal stromal cells. Based on the data presented herein, we conclude that PTHrP excreted by GCT stromal cells increases bone tumor cell local invasiveness and migration., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background and Objectives: Extremity soft tissue sarcomas (STS) are managed with radiotherapy and limb-sparing surgery however aggressive or recurrent cases require amputation. Hyperthermic isolated limb perfusion (HILP) has been proposed as an alternative. Our aim was to systematically review phase II HILP trials, assess tumor response, limb salvage (LS), and quality of scientific publications on this technique., Methods: We conducted a literature search of electronic databases (MEDLINE, EMBASE, Scopus, Cochrane Library) and clinical trial registries for phase II HILP trials on non-resectable extremity STS. Outcomes of interest were complete response (CR), partial response (PR), and LS rates. Quality of published trials was assessed using a quality checklist., Results: Of 518 patients across 12 studies, 408 had some response (CR or PR), and 428 had the limb spared. Median CR, PR, and LS rates were 31%, 53.5%, and 82.5%, respectively. Median Wieberdink loco-regional toxicity rates were 3.8%, 45.5%, 17%, 1%, and 0% for levels 1-5, respectively. No trial fulfilled either all ideal or essential quality criteria. Seven trials did not include statistical methodology., Conclusion: HILP seems effective in treating advanced extremity STS. However, poor publication quality hinders results validity. Technical and methodological standardization, well-designed, multi-institutional trials are warranted., (Copyright © 2012 Wiley Periodicals, Inc.)

Primary perivascular epithelioid cell neoplasms (PEComas) of bone are rare mesenchymal tumors. Histologically, they are composed predominantly of perivascular epithelioid cells and have the capacity to metastasize. PEComas have been reported within intra-abdominal and intra-pelvic organs. To the best of our knowledge, only seven primary PEComas of bone have been described in the English literature. We present two cases of PEComa of bone, one arising from the distal fibula and one from the acetabulum. Both were treated by surgical excision and one also received adjuvant chemotherapy.

Giant cell tumor of bone (GCT) is an aggressive skeletal tumor characterized by local bone destruction, high recurrence rates, and metastatic potential. Previous works in our laboratory, including functional assays, have shown that neutralization of parathyroid hormone-related protein (PTHrP) in the cell environment inhibits cell proliferation and induces cell death in GCT stromal cells, indicating a role for PTHrP in cell propagation and survival. The objective of this study was to investigate the global gene and protein expression patterns of GCT cells in order to identify the underlying pathways and mechanisms of neoplastic proliferation provided by PTHrP in the bone microenvironment. Primary stromal cell cultures from 10 patients with GCT were used in this study. Cells were exposed to optimized concentrations of either PTHrP peptide or anti-PTHrP neutralizing antiserum and were analyzed with both cDNA microarray and proteomic microarray assays in triplicate. Hierarchical clustering and principal component analyses confirmed that counteraction of PTHrP in GCT stromal cells results in a clear-cut gene expression pattern distinct from all other treatment groups and the control cell line human fetal osteoblast (hFOB). Multiple bioinformatics tools were used to analyze changes in gene/protein expression and identify important gene ontologies and pathways common to this anti-PTHrP-induced regulatory gene network. PTHrP neutralization interferes with multiple cell survival and apoptosis signaling pathways by triggering both death receptors and cell cycle-mediated apoptosis, particularly via the caspase pathway, TRAIL pathway, JAK-STAT signaling pathway, and cyclin E/CDK2-associated G1/S cell cycle progression. These findings indicate that PTHrP neutralization exhibits anticancer potential by regulating cell-cycle progression and apoptosis in bone tumor cells, with the corollary being that PTHrP is a pro-neoplastic factor that can be targeted in the treatment of bone tumors., (Copyright © 2012 American Society for Bone and Mineral Research.)

Background: Radiation-induced soft tissue sarcomas (RI-STS) are rare, and it is believed that they are associated with a poor prognosis.The authors of this report compared the clinical and functional outcomes of adults who had extremity RI-STS with the outcomes of adults with sporadic STS., Methods: Forty-four patients who were diagnosed with RI-STS from 1989 to 2009 were identified from 4 prospectively collected databases. Patient demographics, surgical and adjuvant treatment parameters, and oncologic and functional outcomes were evaluated., Results: The median latent period from irradiation of the primary condition to RI-STS diagnosis was 16 years. The median radiotherapy dose used for the index condition was 45 gray. The median age at RI-STS diagnosis was 56 years. The most common primary diagnoses were breast cancer (36.4%) and lymphoma (34.1%). The most common RI-STS histologies were malignant fibrous histiocytoma (36.4%) and angiosarcoma (18.2%). Forty-two patients underwent surgery, 13 patients received adjuvant radiotherapy, and 8 patients received adjuvant chemotherapy. Systemic metastases occurred in 50% of treated patients (n = 21), and 26% (n = 11) developed local recurrence, the risk of which was lower among patients who received reirradiation (P = .043). The 5-year disease-free interval (DFI) and overall survival (OS) rates for patients with RI-STS who presented without metastasis were 36% and 44%, respectively. Patients who had International Union Against Cancer TNM stage III RI-STS had a significantly worse DFI compared with patients who had stage III sporadic STS (multivariate analysis, P = .051). Eighteen patients with RI-STS underwent functional assessment after surgery, and their results were comparable to those of patients with sporadic STS., Conclusions: Despite aggressive surgical treatment, patients who have RI-STS remain at greater risk of both local and systemic recurrence compared with patients who have sporadic STS, but they can anticipate similar functional outcomes. Reirradiation can be relatively safe and effective if used properly., (Copyright © 2011 American Cancer Society.)

Soft-tissue sarcomas spread predominantly to the lung and it is unclear how often FDG-PET scans will detect metastases not already obvious by chest CT scan or clinical examination. Adult limb and body wall soft-tissue sarcoma cases were identified retrospectively. Ewing's sarcoma, rhabdomyosarcoma, GIST, desmoid tumors, visceral tumors, bone tumors, and retroperitoneal sarcomas were excluded as were patients imaged for followup, response assessment, or recurrence. All patients had a diagnostic chest CT scan. 109 patients met these criteria, 87% of which had intermediate or high-grade tumors. The most common pathological diagnoses were leiomyosarcoma (17%), liposarcoma (17%), and undifferentiated or pleomorphic sarcoma (16%). 98% of previously unresected primary tumors were FDG avid. PET scans were negative for distant disease in 91/109 cases. The negative predictive value was 89%. Fourteen PET scans were positive. Of these, 6 patients were already known to have metastases, 3 were false positives, and 5 represented new findings of metastasis (positive predictive value 79%). In total, 5 patients were upstaged by FDG-PET (4.5%). Although PET scans may be of use in specific circumstances, routine use of FDG PET imaging as part of the initial staging of soft-tissue sarcomas was unlikely to alter management in our series.

Purpose: To evaluate inter- and intra-observer variability in gross tumor volume definition for adult limb/trunk soft tissue sarcomas., Patients and Methods: Imaging studies of 15 patients previously treated with preoperative radiation were used in this study. Five physicians (radiation oncologists, orthopedic surgeons and a musculoskeletal radiologist) were asked to contour each of the 15 tumors on T1-weighted, gadolinium-enhanced magnetic resonance images. These contours were drawn twice by each physician. The volume and center of mass coordinates for each gross tumor volume were extracted and a Boolean analysis was performed to measure the degree of volume overlap., Results: The median standard deviation in gross tumor volumes across observers was 6.1% of the average volume (range: 1.8%-24.9%). There was remarkably little variation in the 3D position of the gross tumor volume center of mass. For the 15 patients, the standard deviation of the 3D distance between centers of mass ranged from 0.06 mm to 1.7 mm (median 0.1mm). Boolean analysis demonstrated that 53% to 90% of the gross tumor volume was common to all observers (median overlap: 79%). The standard deviation in gross tumor volumes on repeat contouring was 4.8% (range: 0.1-14.4%) with a standard deviation change in the position of the center of mass of 0.4mm (range: 0mm-2.6mm) and a median overlap of 93% (range: 73%-98%)., Conclusion: Although significant inter-observer differences were seen in gross tumor volume definition of adult soft-tissue sarcoma, the center of mass of these volumes was remarkably consistent. Variations in volume definition did not correlate with tumor size. Radiation oncologists should not hesitate to review their contours with a colleague (surgeon, radiologist or fellow radiation oncologist) to ensure that they are not outliers in sarcoma gross tumor volume definition. Protocols should take into account variations in volume definition when considering tighter clinical target volumes., (Copyright © 2011 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Background: Extracortical bone bridging for treatment of massive bone loss can improve stability and longevity of massive endoprostheses. Osteogenic protein-1 (OP-1), when used with allograft bone, reportedly improves extracortical bone bridging and bone ingrowth., Questions/purposes: We asked whether OP-1 delivered by hydroxyapatite (HA) without bone grafting could improve bone ingrowth and bone formation in the context of extracortical bone bridging., Methods: We implanted unilateral segmental femoral diaphyseal replacement prostheses in 18 dogs (three groups of six dogs). The groups consisted of an HA-coated group augmented with OP-1, an HA-coated group, and a plain porous group. Bone grafting techniques were not used to augment bone formation. The implants were retrieved at 12 weeks for histologic assessment., Results: After removing one specimen owing to a complication, 17 femora were analyzed (six HA-coated augmented with OP-1, five HA-coated, and six plain). We observed better bone ingrowth in the HA-coated OP-1 group than in the plain porous and HA-coated groups, with no difference between the latter two groups. There also was better bone apposition and callus height in the HA-coated OP-1 group than in the plain group but no differences between the HA-coated OP-1 and HA-coated groups or between the HA-coated and plain groups., Conclusions: OP-1 (2.9 mg) delivered by HA-coated segmental replacement prostheses in this canine extracortical bone bridging model revealed improved bone ingrowth over HA-coated implants without OP-1 or plain porous-coated prostheses.

Giant Cell Tumor of Bone (GCT) is an aggressive skeletal tumor characterized by local bone destruction, high recurrence rates and metastatic potential. Previous work in our lab has shown that the neoplastic cell of GCT is a proliferating pre-osteoblastic stromal cell in which the transcription factor Runx2 plays a role in regulating protein expression. One of the proteins expressed by these cells is parathyroid hormone-related protein (PTHrP). The objectives of this study were to determine the role played by PTHrP in GCT of bone with a focus on cell proliferation and apoptosis. Primary stromal cell cultures from 5 patients with GCT of bone and one lung metastasis were used for cell-based experiments. Control cell lines included a renal cell carcinoma (RCC) cell line and a human fetal osteoblast cell line. Cells were exposed to optimized concentrations of a PTHrP neutralizing antibody and were analyzed with the use of cell proliferation and apoptosis assays including mitochondrial dehydrogenase assays, crystal violet assays, APO-1 ELISAs, caspase activity assays, flow cytometry and immunofluorescent immunohistochemistry. Neutralization of PTHrP in the cell environment inhibited cell proliferation in a consistent manner and induced apoptosis in the GCT stromal cells, with the exception of those obtained from a lung metastasis. Cell cycle progression was not significantly affected by PTHrP neutralization. These findings indicate that PTHrP plays an autocrine/paracrine neoplastic role in GCT by allowing the proliferating stromal cells to evade apoptosis, possibly through non-traditional caspase-independent pathways. Thus PTHrP neutralizing immunotherapy is an intriguing potential therapeutic strategy for this tumor.

Background and Purpose. Lymphoedema is a serious complication following limb salvage for extremity soft tissue sarcomas (STSs) for which little is known. We aimed to evaluate its incidence, its, severity and its associated risk factors. Material and Method. Patient and tumor characteristics, treatment modalities and complications and functional outcomes (MSTS 1987, TESS), and lymphoedema severity (Stern) were all collected from prospective databases. Charts were retrospectively abstracted for BMI and comorbidities. Results. There were 289 patients (158 males). Mean age was 53 (16-88). Followup ranged between 12 and 60 months with an average of 35 and a median of 36 months. Mean BMI was 27.4 (15.8-52.1). 72% had lower extremity tumors and 38% upper extremity. Mean tumor size was 8.1 cm (1.0-35.6 cm). 27% had no adjuvant radiation, 62% had 50 Gy, and 11% received 66 Gy. The incidence of lymphoedema was 28.8% (206 none, 58 mild, 22 moderate, 3 severe, and 0 very severe). Mean MSTS score was 32 (11-35) and TESS was 89.4 (32.4-100). Radiation dose was significantly correlated with tumor size > 5 cm (P = 0.0001) and TESS score (P = 0.001), but not MSTS score (P = 0.090). Only tumor size > 5 cm and depth were found to be independent predictors of significant lymphoedema. Conclusion. Nine percent of STS patients in our cohort developed significant (grade ≥ 2) lymphoedema. Tumor size > 5 cm and deep tumors were associated with an increased occurrence of lymphoedema but not radiation dosage.

Matrix-metalloproteinase-13 (MMP-13) has been shown to be an important protease in inflammatory and neoplastic conditions of the skeletal system. In particular, the stromal cells of giant cell tumor of bone (GCT) express very high levels of MMP-13 in response to the cytokine-rich environment of the tumor. We have previously shown that MMP-13 expression in these cells is regulated, at least in part, by the RUNX2 transcription factor. In the current study, we identify the expression of the c-Fos and c-Jun elements of the AP-1 transcription factor in these cells by protein screening assays and real-time PCR. We then used siRNA gene knockdown to determine that these elements, in particular c-Jun, are upstream regulators of MMP-13 expression and activity in GCT stromal cells. We conclude that there was no synergy found between RUNX2 and AP-1 in the regulation of the MMP13 expression and that these transcription factors may be independently regulated in these cells.

Purpose: To report radiological and pathological response to neo-adjuvant radiotherapy for extremity and trunk soft-tissue sarcomas., Materials/methods: Fifty patients were identified retrospectively. All patients had MRI imaging pre and post neo-adjuvant external beam radiotherapy. Tumor volumes were measured in 3D on T1 Gadolinium enhanced sequences. Pathological treatment response was quantified in terms of percentage of treatment-related necrosis for each case., Results: Histopathologic responses to treatment varied from 0% to 100%. The median pathological treatment response was 67.5% for low-grade sarcomas and 50% for high-grade sarcomas. The median decrease in tumor volume was 13.8% for non-myxoid low-grade sarcomas, 82.1% for myxoid liposarcomas and <1% for high-grade sarcomas. A partial response on MRI (volume reduction ≥50%) was highly predictive of a good pathological response (p<0.001). Patients with stable disease on imaging or volumetric progression had wide ranging pathological responses., Conclusions: Soft-tissue sarcomas show significant pathological treatment responses in the form of hyaline fibrosis, necrosis and granulation tissue. Despite this, there is minimal early volumetric response to radiation, especially for high-grade tumors. Although radiological partial response was predictive of pathological response, the significance of radiological progression was unclear. Myxoid liposarcoma tumor type was predictive of both pathological and radiological tumor response., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: Soft-tissue sarcoma spreads predominantly to the lung. The frequency with which positron-emission tomography (pet) detects metastases not already obvious by chest computed tomography (ct) or clinical examination is currently unclear., Methods: We retrospectively identified cases of soft-tissue sarcoma. Ewing sarcoma, rhabdomyosarcoma, and gastrointestinal stromal tumour were excluded, as were cases in which patients underwent imaging for follow-up, response assessment, or recurrence. Patients all had undergone diagnostic chest ct as part of their staging. Directed studies were requested to follow up on abnormal findings in the clinical history or physical examination. All charts and pre-treatment imaging were reviewed retrospectively., Results: From 2004 to 2008, 75 patients met the criteria for the present review. Their median age was 51 years. In 21% of cases, the primary tumour had been removed (by excisional biopsy or unplanned excision) before staging. Of the previously unresected primary tumours, 97% were avid for fluorodeoxyglucose. Of all tumours, 81% were intermediate or high grade (Fédération Nationale des Centres de Lutte Contre le Cancer grades 2-3). The primary tumour was stage T2b in 69% of cases. The most common primary site was a lower extremity (55%). The most common pathologic diagnoses were leiomyosarcoma (21%), liposarcoma (19%), and synovial sarcoma (17%). At the end of staging, 17% of patients were considered to have metastatic disease. Imaging by pet was negative for distant disease in 64 of the 75 cases. In 7 of the 64 cases, metastatic disease was evident on chest ct (negative predictive value: 88%). Imaging by pet was positive in 8 cases, with 5 of those already known to have metastases, 2 having pathologically proven false positives, and 1 being a new finding of a pulmonary metastasis (positive predictive value: 75%). The pet imaging was indeterminate in 3 patients (none of whom subsequently developed metastatic disease). Two incidental benign parotid tumours were found. Overall, only 1 patient was upstaged as a result of pet imaging (1.3%). In addition, pet did not alter the management of patients already know to have M1 disease (no new organ sites identified)., Conclusions: Although pet may be helpful in specific circumstances, routine use of fluorodeoxyglucose pet imaging for detection of metastatic disease as part of the initial staging of soft-tissue sarcoma added little to imaging by chest ct and was unlikely to alter management in our series.