Extended distal femur resection: Megaprosthesis with telescopic bone allograft augmentation versus total femur prosthesis.

BACKGROUND AND OBJECTIVE: Oncological distal femur resections can leave a proximal femur too short to host a stem. Reconstructive techniques are then challenging. The purpose of the study is to compare implant survival, complication rate and MSTS of two different options. METHODS: We retrospectively divided 33 patients with primary bone tumours of distal femur in Group 1 (16 patients reconstructed with knee megaprosthesis with proximal bone augmentation, APC) and Group 2 (17 patients reconstructed with total femur prosthesis, TFP). Less than 12 cm of remaining proximal femur were planned for all resections. RESULTS: MSTS score at 2 years is 25 ± 5 for Group 1 and 19 ± 7 for Group 2 (confidence interval [C.I.] 95%, p = 0.02). At 5 years it is 27 ± 2 for Group 1 and 22 ± 6 for Group 2 (C.I. 95%, p = 0.047). Failure and complication rates are lower for Group 1, but no statistical significance was reached. In APC reconstruction, union at the host-allograft junction was achieved in 16 out of 16 patients using the telescopic bone augmentation technique. CONCLUSIONS: APC provides higher functional results compared to TFP after extended distal femur resection. In APC reconstruction, telescopic augmentation is excellent for achieving union at the host-allograft junction.

Diagnostic challenges in low-grade central osteosarcoma.

Aims: Low-grade central osteosarcoma (LGCOS), a rare type of osteosarcoma, often has misleading radiological and pathological features that overlap with those of other bone tumours, thereby complicating diagnosis and treatment. We aimed to analyze the clinical, radiological, and pathological features of patients with LGCOS, with a focus on diagnosis, treatment, and outcomes. Methods: We retrospectively analyzed the medical records of 49 patients with LGCOS (Broder's grade 1 to 2) treated between January 1985 and December 2017 in a single institute. We examined the presence of malignant features on imaging (periosteal reaction, cortical destruction, soft-tissue invasion), the diagnostic accuracy of biopsy, surgical treatment, and oncological outcome. Results: Based on imaging, 35 of 49 patients (71.4%) exhibited malignant features. Overall, 40 of 49 patients (81.6%) had undergone a biopsy before en-bloc resection: 27 of 40 patients (67.5%) were diagnosed on the first biopsy, which was more accurate when carried out by open rather than needle biopsy (91.3% vs 35.3% diagnostic accuracy, respectively; p < 0.001). Of the 40 patients treated by en-bloc resection, surgical margins were wide in 38 (95.0%) and marginal in two (5.0%). Furthermore, nine of 49 patients (18.4%) underwent curettage (intralesional margin) without previous biopsy. All patients with a positive margin developed local recurrence. Distant metastases occurred in five of 49 patients (10.2%). The mean five-year overall survival (OS) and distant relapse-free survival (D-RFS) were 89.3% (SD 5.1%) and 85.7% (SD 5.5%), respectively. Univariate analysis showed that the occurrence of distant metastasis was a poor prognostic factor for OS (hazard ratio 11.54, 95% confidence interval (CI) 1.92 to 69.17; p < 0.001). Local recurrence was a poor prognostic factor for D-RFS (HR 8.72, 95% CI 1.69 to 45.0; p = 0.002). Conclusion: The diagnosis of LGCOS can be challenging because it may present with non-malignant features and has a low diagnostic accuracy on biopsy. If precisely diagnosed, LGCOS can be successfully treated by surgical excision with wide margins.

Aneurysmal bone cyst: Is selective arterial embolization effective as curettage and bone grafting?

INTRODUCTION: Aneurysmal bone cyst (ABC) is a lytic benign bone lesion representing about 1% of all primary bone tumors. Method to treat ABC's have developed over time. The standard of care cure for ABC has been curettage with or without bone grafting of the defect but is burdened by recurrence rates of approximately 25%-31%. Based on the assumption that ABCs usually supplied by one or more pathological feeding arteries, selective arterial embolization has been described as an adjuvant preoperative procedure to reduce intra-operative hemorrhage, and as primary treatment for lesions in difficult surgical access. In the current study, we therefore asked whether (1) a single or a repeat selective arterial embolization (SAE) for treating ABCs would produce comparable healing rates compared with curettage and bone grafting; (2) evaluated the relationship of recurrence in relation to the site of the cyst, the age, and gender of the patients; and (3) the two techniques differ in term of long-term complication. MATERIAL AND METHODS: We retrospectively reviewed 265 patients who underwent curettage and bone grafting or SAE performed at our institute from 1994 to 2018. The diagnosis of ABC was always established with percutaneous CT-guided biopsy or open biopsy. Patients were followed clinically with plain radiographs or CT scan at 3, 6, 9, and 12 months then annually in the absence of symptoms. Treatment success was determined evaluating pre- and postprocedural imaging according to Chang classification. RESULTS: Two hundred and nineteen were treated with curettage and bone grafting (curettage group), and 46 with SAE Group. Of the 219 patients treated with Curettage and bone grafting (curettage group), 165 out of 219 (75.3%) experienced bone healing, while local recurrence was observed in 54 cases (24.7%) after 12 months on average (range: 3-120 months) from surgery. After the first SAE, bone ossification was seen in 27 (58.7%), without needing any further treatment. Eleven recurred patients were treated with SAE (four patients need two while seven need three SAE to heal), and eight patients with curettage and bone grafting. Thirty-eight out of 46 (82%) patients experienced bone ossification regardless the number of SAE. The overall rate of local recurrence for all patients was 26.7%. SAE group presented a lower complication rate (6%) where two patients experienced skin necrosis, and one limb-length discrepancies (2% of all cohort). DISCUSSION: The use of SAE is an attractive option to treat ABC as it combines on one hand a lower complication rate than curettage and bone grafting, on the other it can be carried out in case of nonresectable ABCs, significantly reducing the size of viable ABC lesions, fostering bone remodeling and mineralization, and most importantly, significantly improving the patient's quality of life.

Total hip arthroplasty in hereditary multiple exostosis patients: literature review and evaluation of 10 cases.

BACKGROUND: Acquired hip deformities in patients affected by hereditary multiple exostosis (HME) may incur in early hip osteoarthritis and functional limitation requiring primary total hip arthroplasty (THA). Characteristic coxo-femoral joint dysmorphisms in HME may pose a challenge for the orthopaedic surgeon. Here we report our experience in a series of patients with HME treated in our hospital with THA. METHODS: With a mean follow-up of 5 years, 10 primary THAs were reviewed; proximal femur deformities, acetabular dysplasia and joint osteoarthritis has been assessed through x-rays and CT-scan evaluation. In all cases hemispheric press-fit cups were used; 4 stem had metaphyseal engagement, 5 had proximal diaphyseal engagement and 1, with anatomical geometry, had metaphyseal fixation. 2 cases required stem cementation, 3 modular neck and 1 lateralised. The clinical data, complications and clinical outcomes, were recorded and analysed. RESULTS: The mean Harris Hip Score (HHS) increased from 34 preoperative to 86 postoperative; preoperative mean neck shaft angle (NSA) was 150°, head/neck ratio 0.6, offset 31 mm; Wiberg angle 28°, Sharp angle 38°, 1 patient had subluxation grade 4 according to Crowe, 8 hips showed osteoarthritis (Tönnis grade ⩾2 ); 5 femurs were classified as Dorr type C, 2 as type B and 3 as type A. Perioperative complications were not observed. CONCLUSIONS: Primary THA in HME significantly improved clinical and functional outcomes. Press-fit cup fixation together with metaphyseal and proximal diaphyseal stem engagement on reliable bone quality femur, represents a valid option in HME patients with normal acetabular morphology, wide broaden neck and valgus NSA.

Phase 2 study for nonmetastatic extremity high-grade osteosarcoma in pediatric and adolescent and young adult patients with a risk-adapted strategy based on ABCB1/P-glycoprotein expression: An Italian Sarcoma Group trial (ISG/OS-2).

BACKGROUND: According to retrospective osteosarcoma series, ABCB1/P-glycoprotein (Pgp) overexpression predicts for poor outcomes. A prospective trial to assess a risk-adapted treatment strategy using mifamurtide in Pgp+ patients was performed. METHODS: This was a phase 2, multicenter, uncontrolled trial including patients 40 years old or younger with nonmetastatic extremity high-grade osteosarcoma stratified according to Pgp expression. All patients received high-dose methotrexate, doxorubicin, and cisplatin (MAP) preoperatively. In Pgp+ patients, mifamurtide was added postoperatively and combined with MAP for a good histologic response (necrosis ≥ 90%; good responders [GRs]) or with high-dose ifosfamide (HDIFO) at 3 g/m2 /d on days 1 to 5 for a histologic response < 90% (poor responders [PRs]). Pgp- patients received MAP postoperatively. After an amendment, the cumulative dose of methotrexate was increased from 60 to 120 g/m2 (from 5 to 10 courses). The primary end point was event-free survival (EFS). A postamendment analysis was performed. RESULTS: In all, 279 patients were recruited, and 194 were included in the postamendment analysis: 70 (36%) were Pgp-, and 124 (64%) were Pgp+. The median follow-up was 51 months. For Pgp+ patients, 5-year EFS after definitive surgery (null hypothesis, 40%) was 69.8% (90% confidence interval [CI], 62.2%-76.2%): 59.8% in PRs and 83.7% in GRs. For Pgp- patients, the 5-year EFS rate was 66.4% (90% CI, 55.6%-75.1%). CONCLUSIONS: This study showed that adjuvant mifamurtide, combined with HDIFO for a poor response to induction chemotherapy, could improve EFS in Pgp+ patients. Overall, the outcomes compared favorably with previous series. Mifamurtide and HDIFO as salvage chemotherapy are worth further study.

The Rizzoli Multiple Osteochondromas Classification revised: describing the phenotype to improve clinical practice.

Multiple osteochondromas (MO) is a rare disorder, characterized by benign osteocartilaginous tumors (osteochondromas), arising from the perichondrium of bones. The osteochondromas increase during growth, frequently causing deformities and limitations. Our study aims to analyze the data captured by the Registry of Multiple Osteochondromas, to refine Istituto Ortopedico Rizzoli (IOR) Classification, providing a representative picture of the phenotypic manifestations throughout the lifespan. We conducted a single-institution cross-sectional study. Patients were categorized according to IOR Classification, which identifies three patients' classes on the presence/absence of deformities and/or limitations. The present dataset was compared with our previously published data, to refine the classification. Nine hundred sixty-eight patients were included: 243 children (<10 years), 136 adolescents (10-15 years), and 589 adults. Of the entire population, half patients presented at least one deformity, and one quarter reported at least one limitation. Compared with our previous study, the amount of children was more than doubled and the percentage of mild/moderate cases was notably increased, giving a better disease overview throughout the lifespan and suggesting a different cut-off for dividing Class II in subclasses. We confirmed that MO is characterized by phenotypic heterogeneity, suggesting that an early classification of the disease may offer a useful tool to follow disease pattern and evolution, to support clinical practice, and to propose timely interventions.

Minimally invasive treatment of long bone non-unions with bone marrow concentrate, demineralized bone matrix and platelet-rich fibrin in 38 patients.

To determine the efficacy of percutaneous injection of autologous bone marrow concentrated (BMC), demineralized bone matrix (DBM), and platelet rich fibrin (PRF) in the treatment of long bone non-unions. From January 2011 to January 2018 patients with non-union of the lower limbs who were on the waiting list for open grafting with established tibial or femoral non-union and minimal deformity were eligible to participate in this study. Patients were treated with a single percutaneous injection of DBM, BMC and PRF. Our study group comprised 38 patients (26 males and 12 females; mean age 39, range 18 to 65). Non-unions were located in the femur (18 cases) and in the tibia (20 cases). Clinical and imaging follow-up ranged from 4 to 60 months (mean 20 months). Bone union occurred in 30 out of 38 patients (79%) in an average of 7 months (range 3 to 12) and all healed patients had full weight bearing after 9 months on average (range 6 to 12) from injection. In 19 cases the osteosynthesis was removed 12 months on average (range 3 to 36) from surgery. One patient developed infection at the non-union site after treatment. Percutaneous injection of DBM, BMC, and PRF is an effective treatment for long-bone non-unions. This technique allows the bone to heal with a minimally invasive approach and with a hospitalization of 2 days. Key elements of bone regeneration consist of a combination of biological and biomechanical therapeutic approach.

Outcome in dedifferentiated chondrosarcoma for patients treated with multimodal therapy: Results from the EUROpean Bone Over 40 Sarcoma Study.

INTRODUCTION: The role of chemotherapy for patients with dedifferentiated chondrosarcoma (DDCS) is still under discussion. Here, we present the outcome in patients with DDCS treated with intensive chemotherapy from the EUROpean Bone Over 40 Sarcoma Study. MATERIALS AND METHODS: The chemotherapy regimen included doxorubicin, ifosfamide and cisplatin. Postoperative methotrexate was added in case of poor histological response. Toxicity was graded based on the National Cancer Institute expanded common toxicity criteria, version 2.0, and survival was analysed using Kaplan-Meier curves, log-rank tests and univariate Cox regression models. RESULTS: Fifty-seven patients with DDCS (localised, 34 [60%]; metastatic, 23 [40%]) aged 42-65 years were included. Surgical complete remission (SCR) was achieved in 36 (63%) patients. The median overall survival (OS) was 24 months (95% confidence interval, 22-25), and the 5-year OS was 39%. Patients with extremity localisation had a 5-year OS of 49% compared with 29% in patients with a central tumour (P = 0.08). Patients with localised disease had a 5-year OS of 46%, whereas patients with metastatic disease had a 5-year OS of 29% (P = 0.12). Patients in SCR had a 5-year OS of 49%, whereas patients not in SCR had a 5-year OS of 23% (P = 0.004). Chemotherapy toxicity was considerable but manageable. There was no treatment-related death, and 39 (70%) patients received ≥6 cycles of the planned nine chemotherapy cycles. CONCLUSIONS: Adding intensive chemotherapy to surgery for treatment of DDCS is feasible and shows favourable survival data compared with previous reports. With the limitations of data from a non-controlled trial, we conclude that chemotherapy could be considered in the management of patients aged >40 years.

C-reactive protein and tumour diagnosis predict survival in patients treated surgically for long bone metastases.

PURPOSE: Surgical options for long bone metastases include intramedullary nail fixation or prosthetic reconstruction. Patients with a short life expectancy may benefit from less invasive surgery such as intramedullary nail fixation, while patients with a long life expectancy could be treated with more invasive surgery such as prosthetic reconstruction. The purpose of our study was to analyze the survival of patients treated surgically for long bone metastases, determining the prognostic factors affecting survival and analyzing the surgical complications and reoperation rates. Based on our results, we developed a prognostic score that helps to choose the best treatment for these patients. In addition, we compared the performance of our prognostic score with other previous prognostic models. METHOD: We investigated prospectively potential clinical and laboratory prognostic factors in 159 patients with metastatic bone disease who underwent surgery with intramedullary nail fixation or prosthetic reconstruction. Clinical data were collected, recording the following data: age and sex of patients, primary tumour and time of diagnosis, number (single or multiple) and presentation (synchronous or metachronous) of bone metastases, presence of visceral metastases. The following laboratory data were analyzed: hemoglobin, leukocyte counts, lymphocyte counts, platelets count, alkaline phosphatase, and C-reactive protein. RESULTS: Our study showed that pathological C-reactive protein and primary tumour diagnosis were significant negative independent prognostic factors at 12-month survival. Based on our results, we created a score using C-reactive protein and primary tumour diagnosis, creating three different prognostic groups: (A) good prognosis primary tumour and physiological CRP with probability of survival at 12 months of 88.9 [80.1-98.5]; (B) bad prognosis primary tumour and physiological CRP or good prognosis primary tumour and pathological CRP with a probability of survival at 12 months of 56.7 [45.4-70.7]; (C) bad prognosis primary tumour and pathological CRP with a probability of survival at 12 months of 12.5 [5.0-28.3]. Using ROC multiple analysis, our score (AUC = 0.816) was the most accurate in predicting a 12-month survival compared to previous prognostic models. DISCUSSION: Patients treated surgically for long bone metastases with a life expectancy over 12 months should be treated with more durable reconstruction, while patients with a life expectancy less than 12 months should be treated with less invasive surgery. The diagnosis of primary cancer and C-reactive protein are two very simple data which every orthopaedic surgeon in any community hospital can easily rely on for any decision-making in the surgical treatment of a complex patient as with a patient with skeletal metastases. CONCLUSION: Our prognostic score based on only two simple variables (C-reactive protein and primary tumour diagnosis) was able to predict the 12-month survival of patients treated surgically for long bone metastases and could be helpful in choosing the best treatment for these patients.

Image-guided Cryotherapy for Musculoskeletal Tumors.

BACKGROUND: This article represents a review of the use of image-guided cryotherapy in the treatment of musculoskeletal tumor lesions. Cryotherapy is able to induce a lethal effect on cancer cells through direct and indirect mechanisms. In this manuscript, we combined our experience with that of other authors who have published on this topic in order to provide indications on when to use cryotherapy in musculoskeletal oncology. DISCUSSION: Image-Guided percutaneous cryotherapy is a therapeutic method now widely accepted in the treatment of patients with musculoskeletal tumors. It can be used both for palliative treatments of metastatic bone lesions and for the curative treatment of benign bone tumors, such as osteoid osteoma or osteoblastoma. In the treatment of bone metastases, cryotherapy plays a major role in alleviating or resolving disease-related pain, but it has also been demonstrated that it can have a role in local disease control. In recent years, the use of cryotherapy has also expanded for the treatment of both benign and malignant soft tissue tumors. CONCLUSION: Percutaneous cryotherapy can be considered a safe and effective technique in the treatment of benign and malignant musculoskeletal tumors. Cryotherapy can be considered the first option in benign tumor lesions, such as osteoid osteoma, and a valid alternative to radiofrequency ablation. In the treatment of painful bone metastases, it must be considered secondarily to other standard treatments (radiotherapy, bisphosphonate therapy, and chemotherapy) when they are no longer effective in controlling the disease or when they cannot be repeated (for example, radiotherapy).

Myxofibrosarcoma: Clinical and Prognostic Value of MRI Features.

Myxofibrosarcoma is one of the most common soft tissue sarcomas in the elderly. It is characterized by an extremely high rate of local recurrence, higher than other soft tissue tumors, and a relatively low risk of distant metastases.Magnetic resonance imaging (MRI) is the imaging modality of choice for the assessment of myxofibrosarcoma, which plays a key role in the preoperative setting of these patients. MRI features associated with the high risk of local recurrence are: high myxoid matrix content (water-like appearance of the lesions), high grade of contrast enhancement and presence of an infiltrative pattern ("tail sign"). On the other hand, MRI features associated with worse sarcoma specific survival are: large size of the lesion, deep location, high grade of contrast enhancement. Recognizing the above-mentioned imaging features of myxofibrosarcoma may be helpful in stratifying the risk for local recurrence and disease-specific survival. Moreover, the surgical planning should be adjusted according to the MRI features.

Different reconstructive techniques for tumours of the distal tibia.

AIMS: The aim of this study was to report the results of three forms of reconstruction for patients with a ditsl tibial bone tumour: an intercalary resection and reconstruction, an osteoarticular reconstruction, and arthrodesis of the ankle. METHODS: A total of 73 patients with a median age of 19 years (interquartile range (IQR) 14 to 36) were included in this retrospective, multicentre study. RESULTS: Reconstructions included intercalary resection in 17 patients, osteoarticular reconstruction in 11, and ankle arthrodesis in 45. The median follow-up was 77 months (IQR 35 to 130). Local recurrence occurred in eight patients after a median of 14 months (IQR 9 to 36), without a correlation with adequacy of margins or reconstructive technique. Major complications included fracture of the graft in ten patients, nonunion of the proximal osteotomy in seven, and infection in five. In the osteoarticular group, three of 11 patients developed radiological evidence of severe osteoarthritis, but only one was symptomatic and required conversion to ankle arthrodesis. Functional evaluation showed higher values of the Musculoskeletal Tumour Society (MSTS) and American Orthopaedic Foot and Ankle Society (AOFAS) scores in the intercalary group compared with the others. CONCLUSION: Preservation of the epiphysis in patients with a distal tibial bone tumour is a safe and effective form of limb-sparing treatment. It requires rigorous preoperative planning after accurate analysis of the imaging. When joint-sparing resection is not indicated, ankle arthrodesis, either isolated tibiotalar or combined tibiotalar and subtalar arthrodesis, should be preferred over osteoarticular reconstruction. Cite this article: Bone Joint J 2020;102-B(11):1567-1573.

How Does the Skeletal Oncology Research Group Algorithm's Prediction of 5-year Survival in Patients with Chondrosarcoma Perform on International Validation?

BACKGROUND: The Skeletal Oncology Research Group (SORG) machine learning algorithm for predicting survival in patients with chondrosarcoma was developed using data from the Surveillance, Epidemiology, and End Results (SEER) registry. This algorithm was externally validated on a dataset of patients from the United States in an earlier study, where it demonstrated generally good performance but overestimated 5-year survival. In addition, this algorithm has not yet been validated in patients outside the United States; doing so would be important because external validation is necessary as algorithm performance may be misleading when applied in different populations. QUESTIONS/PURPOSES: Does the SORG algorithm retain validity in patients who underwent surgery for primary chondrosarcoma outside the United States, specifically in Italy? METHODS: A total of 737 patients were treated for chondrosarcoma between January 2000 and October 2014 at the Italian tertiary care center which was used for international validation. We excluded patients whose first surgical procedure was performed elsewhere (n = 25), patients who underwent nonsurgical treatment (n = 27), patients with a chondrosarcoma of the soft tissue or skull (n = 60), and patients with peripheral, periosteal, or mesenchymal chondrosarcoma (n = 161). Thus, 464 patients were ultimately included in this external validation study, as the earlier performed SEER study was used as the training set. Therefore, this study-unlike most of this type-does not have a training and validation set. Although the earlier study overestimated 5-year survival, we did not modify the algorithm in this report, as this is the first international validation and the prior performance in the single-institution validation study from the United States may have been driven by a small sample or non-generalizable patterns related to its single-center setting. Variables needed for the SORG algorithm were manually collected from electronic medical records. These included sex, age, histologic subtype, tumor grade, tumor size, tumor extension, and tumor location. By inputting these variables into the algorithm, we calculated the predicted probabilities of survival for each patient. The performance of the SORG algorithm was assessed in this study through discrimination (the ability of a model to distinguish between a binary outcome), calibration (the agreement of observed and predicted outcomes), overall performance (the accuracy of predictions), and decision curve analysis (establishment on the ability of a model to make a decision better than without using the model). For discrimination, the c-statistic (commonly known as the area under the receiver operating characteristic curve for binary classification) was calculated; this ranged from 0.5 (no better than chance) to 1.0 (excellent discrimination). The agreement between predicted and observed outcomes was visualized with a calibration plot, and the calibration slope and intercept were calculated. Perfect calibration results in a slope of 1 and an intercept of 0. For overall performance, the Brier score and the null-model Brier score were calculated. The Brier score ranges from 0 (perfect prediction) to 1 (poorest prediction). Appropriate interpretation of the Brier score requires comparison with the null-model Brier score. The null-model Brier score is the score for an algorithm that predicts a probability equal to the population prevalence of the outcome for every patient. A decision curve analysis was performed to compare the potential net benefit of the algorithm versus other means of decision support, such as treating all or none of the patients. There were several differences between this study and the earlier SEER study, and such differences are important because they help us to determine the performance of the algorithm in a group different from the initial study population. In this study from Italy, 5-year survival was different from the earlier SEER study (71% [319 of 450 patients] versus 76% [1131 of 1487 patients]; p = 0.03). There were more patients with dedifferentiated chondrosarcoma than in the earlier SEER study (25% [118 of 464 patients] versus 8.5% [131 of 1544 patients]; p < 0.001). In addition, in this study patients were older, tumor size was larger, and there were higher proportions of high-grade tumors than the earlier SEER study (age: 56 years [interquartile range {IQR} 42 to 67] versus 52 years [IQR 40 to 64]; p = 0.007; tumor size: 80 mm [IQR 50 to 120] versus 70 mm [IQR 42 to 105]; p < 0.001; tumor grade: 22% [104 of 464 had Grade 1], 42% [196 of 464 had Grade 2], and 35% [164 of 464 had Grade 3] versus 41% [592 of 1456 had Grade 1], 40% [588 of 1456 had Grade 2], and 19% [276 of 1456 had Grade 3]; p ≤ 0.001). RESULTS: Validation of the SORG algorithm in a primarily Italian population achieved a c-statistic of 0.86 (95% confidence interval 0.82 to 0.89), suggesting good-to-excellent discrimination. The calibration plot showed good agreement between the predicted probability and observed survival in the probability thresholds of 0.8 to 1.0. With predicted survival probabilities lower than 0.8, however, the SORG algorithm underestimated the observed proportion of patients with 5-year survival, reflected in the overall calibration intercept of 0.82 (95% CI 0.67 to 0.98) and calibration slope of 0.68 (95% CI 0.42 to 0.95). The Brier score for 5-year survival was 0.15, compared with a null-model Brier of 0.21. The algorithm showed a favorable decision curve analysis in the validation cohort. CONCLUSIONS: The SORG algorithm to predict 5-year survival for patients with chondrosarcoma held good discriminative ability and overall performance on international external validation; however, it underestimated 5-year survival for patients with predicted probabilities from 0 to 0.8 because the calibration plot was not perfectly aligned for the observed outcomes, which resulted in a maximum underestimation of 20%. The differences may reflect the baseline differences noted between the two study populations. The overall performance of the algorithm supports the utility of the algorithm and validation presented here. The freely available digital application for the algorithm is available here: https://sorg-apps.shinyapps.io/extremitymetssurvival/. LEVEL OF EVIDENCE: Level III, prognostic study.

Fibrocartilaginous mesenchymoma of bone: a single-institution experience with molecular investigations and a review of the literature.

AIMS: Fibrocartilaginous mesenchymoma is a rare intraosseous lesion, with a total of 26 cases described in the literature. This study describes the clinical, radiological and histological features of eight new cases of fibrocartilaginous mesenchymoma collected at a single institution between 1982 and 2016. The presence of GNAS and IDH1/2 mutations and MDM2 amplification was explored to evaluate possible links between fibrocartilaginous mesenchymoma, fibrous dysplasia, de-differentiated chondrosarcoma and low-grade osteosarcoma. METHODS AND RESULTS: Eight new cases of fibrocartilaginous mesenchymoma of bone identified in our archives, dating from 1982 to 2016, were reviewed. The diagnosis was not performed on the initial biopsy in any of these cases, due mainly to the absence of obvious cartilaginous differentiation. On imaging, the tumour contained cartilaginous calcifications and showed a very strong uptake of contrast medium after injection. Histologically, the tumour was characterized by spindle cell proliferation mimicking a low-grade spindle cell sarcoma, associated with epiphyseal growth-plate-like nodules of cartilage and bone production. Molecularly, no GNAS and IDH1/2 mutations or MDM2 amplification were found in the cases analysed. Only one case recurred 1 year following intralesional resection. None died of disease. CONCLUSIONS: This very rare bone tumour has a typical radiological and histological pattern and a favourable survival outcome after treatment. Local recurrences can be prevented with complete surgery. Fibrocartilaginous mesenchymoma does not seem to be related genetically to fibrous dysplasia, low-grade osteosarcoma and de-differentiated chondrosarcoma.

Ewing sarcoma in patients over 40 years of age: a prospective analysis of 31 patients treated at a single institution.

PURPOSE: Patients with Ewing sarcoma who are 40 years old or older are usually excluded from clinical trials. For this reason, information on this subset of patients is limited. METHODS: Clinical characteristics and treatment-related variables of patients aged 40 years or more, with a diagnosis of Ewing sarcoma, treated at the authors' institution had been prospectively collected since 1999. RESULTS: Thirty-one patients were identified, with ages ranging from 40 to 70 years (median 45 years). Twenty-six (84%) had localized disease, 4 patients presented with lung metastases, and 1 patient had multiple metastases (bone, lung, abdominal nodes, and bone marrow). The primary tumors were skeletal in 19 (61%) patients, while 12 (39%) had extraskeletal disease. All patients received chemotherapy according to regimens similar to those adopted in younger patients, based on doxorubicin, cyclophosphamide, etoposide, vincristine, dactinomycin, and ifosfamide. All patients experienced grade 4 leukopenia (100%); red blood cells or platelets transfusions were needed in 50% and 16% of patients, respectively. Toxicity-related dose reduction was required in 13 patients (43%). The 5-year overall survival (OS) was 54% for the whole group. In patients with complete remission, 5-year disease-free survival was 57%. Survival was different for patients with skeletal and extraskeletal Ewing sarcoma (5-year OS: 64% vs 40%, p = 0.2). CONCLUSIONS: In older patients, the incidence of extraskeletal Ewing sarcoma is high. Intensive chemotherapy treatment can be recommended in this group. The high chemotherapy toxicity can be justified by expected results, similar to those of younger patients.

Diffuse-type tenosynovial giant cell tumour: Current treatment concepts and future perspectives.

At present, the optimal treatment strategy in patients with diffuse-type tenosynovial giant cell tumour (D-TGCT) is unclear. The purpose of this review was to describe current treatment options, and to highlight recent developments in the knowledge of the molecular pathogenesis of D-TGCT as well as related therapeutic implications. Epidemiology, clinical features, and the pathogenesis of D-TGCT and the most widely used treatment modalities are described. D-TGCT is a benign clonal neoplastic proliferation arising from the synovium. Patients are often symptomatic and require multiple surgical procedures during their lifetime. Currently, surgery is the main treatment for patients with D-TGCT, with relapse rates ranging from 14% to 55%. Radiosynovectomy and external beam radiotherapy have been used in combination with surgical excision or as single modalities. The finding that D-TGCT cells overexpress colony-stimulating factor 1 (CSF1), resulting in recruitment of CSF1 receptor (CSF1R)-bearing macrophages that are polyclonal and make up the bulk of the tumour, has led to clinical trials with CSF1R inhibitors. These inhibitors include small molecules such as imatinib, nilotinib, PLX3397, and the monoclonal antibody RG7155. In conclusion, D-TGCT impairs patients' quality of life significantly. The evidence that the pathogenetic loop of D-TGCT can be inhibited could potentially change the therapeutic armamentarium for this condition. Clinical trials of agents that target D-TGCT are currently ongoing. In the meantime, international registries should be activated in order to provide useful information on this relatively rare tumour.

Paediatric chondrosarcomas: a retrospective review of 17 cases.

AIMS: Chondrosarcoma is primarily a tumour of adulthood and old age. Some studies indicate that survival is worse in paediatric than in adult chondrosarcomas. In view of the rarity of paediatric chondrosarcoma, few large studies are currently available. METHODS AND RESULTS: We evaluated the clinical, radiological and pathological features of a single institution series of chondrosarcomas presenting in patients younger than 17 years between 1981 and 2014. Seventeen patients with central (10), peripheral (five) and periosteal (two) chondrosarcoma were retrieved. The patients received various treatments according to the dimension, stage and grading of the lesions. Only two tumours, treated with resection, recurred after the first diagnosis, at 11 and 108 months, respectively. All patients but one were alive without disease at the time of the last follow-up (median: 148 months). The one patient who died of disease 27 months after diagnosis had a grade 2 central chondrosarcoma of the metacarpal bone. He was affected by Maffucci syndrome and developed multiple bone and lung metastases. CONCLUSIONS: Chondrosarcoma in children is rare but does exist, and is not limited to the head and neck region. Our findings do not support the current view that chondrosarcomas are more aggressive in children than in adults.

3D Bioprinting of Cartilage for Orthopedic Surgeons: Reading between the Lines.

Chondral and osteochondral lesions represent one of the most challenging and frustrating scenarios for the orthopedic surgeon and for the patient. The lack of therapeutic strategies capable to reconstitute the function and structure of hyaline cartilage and to halt the progression toward osteoarthritis has brought clinicians and scientists together, to investigate the potential role of tissue engineering as a viable alternative to current treatment modalities. In particular, the role of bioprinting is emerging as an innovative technology that allows for the creation of organized 3D tissue constructs via a "layer-by-layer" deposition process. This process also has the capability to combine cells and biomaterials in an ordered and predetermined way. Here, we review the recent advances in cartilage bioprinting and we identify the current challenges and the directions for future developments in cartilage regeneration.

Are Complications Associated With the Repiphysis(®) Expandable Distal Femoral Prosthesis Acceptable for Its Continued Use?

BACKGROUND: Reconstruction of the distal femur after resection for malignant bone tumors in skeletally immature children is challenging. The use of megaprostheses has become increasingly popular in this patient group since the introduction of custom-made, expandable devices that do not require surgery for lengthening, such as the Repiphysis(®) Limb Salvage System. Early reports on the device were positive but more recently, a high complication rate and associated bone loss have been reported. QUESTIONS/PURPOSES: We asked: (1) what are the clinical outcomes using the Musculoskeletal Tumor Society (MSTS) scoring system after 5-year minimum followup in patients treated with this prosthesis at one center; (2) what are the problems and complications associated with the lengthening procedures of this implant; and (3) what are the specific concerns associated with revision of this implant? METHODS: At our institute, between 2002 and 2007, the Repiphysis(®) expandable prosthesis was implanted in 15 children (mean age, 8 years; range, 6-11 years) after distal femoral resection for malignant bone tumors. During this time, the general indication for use of this implant was resection of the distal femur for localized malignant bone tumors in pediatric patients. Alternative techniques used for this indication were modular prosthetic reconstruction, massive (osteoarticular or intercalary) allograft reconstruction, or rotationplasty. Age and tumor extension were the main factors to decide on the surgical indication. Of the 15 patients who had this prosthesis implanted during reconstruction surgery, five died with the implant in situ or underwent amputation before 5 years followup and the remaining 10 were evaluated at a minimum of 5 years (mean, 104 months; range, 78-140 months). No patients were lost to followup. These 10 patients were long-term survivors and underwent the lengthening program. They were included in our study analysis. The first seven lengthening procedures were attempted in an outpatient setting; however, owing to pain and burning sensations experienced by the patients, the procedures failed to achieve the desired lengthening. Therefore, other procedures were performed with the patients under general anesthesia. We reviewed clinical data at index surgery for all 15 patients. We further analyzed the lengthening procedures, implant survival, radiographic and functional results, for the 10 long-term survivors. Functional results were assessed according to the MSTS scoring system. Complications were classified according to the International Society of Limb Salvage (ISOLS) classification system. RESULTS: Nine of the 10 survivors underwent revision of the implant for mechanical failure. They had a mean MSTS score of 64% (range, 47%-87%) before revision surgery. At final followup the 10 long-term surviving patients had an average MSTS score of 81% (range, 53%-97%). In total, we obtained an average lengthening of 39 mm per patient (range, 17-67 mm). Exact expansion of the implant was unpredictable and difficult to control. Nine of 10 of the long-term surviving patients underwent revision surgery of the prosthesis-eight for implant breakage and one for stem loosening. At revision surgery, six patients had another type of expandable prosthesis implanted and three had an adult-type megaprosthesis implanted. In five cases, segmental bone grafts were used during revision surgery to compensate for loss of bone stock. CONCLUSIONS: We could not comfortably expand the Repiphysis(®) prosthesis in an outpatient setting because of pain experienced by the patients during the lengthening procedures. Furthermore, use of the prosthesis was associated with frequent failures related to implant breakage and stem loosening. Revisions of these procedures were complex and difficult. We no longer use this prosthesis and caution others against the use of this particular prosthesis design. LEVEL OF EVIDENCE: Level IV, therapeutic study.