Can the Cartilaginous Thickness Determine the Risk of Malignancy in Pelvic Cartilaginous Tumors, and How Accurate is the Preoperative Biopsy of These Tumors?

BACKGROUND: Peripheral osteochondral tumors are common, and the management of tumors presenting in the pelvis is challenging and a controversial topic. Some have suggested that cartilage cap thickness may indicate malignant potential, but this supposition is not well validated. QUESTIONS/PURPOSES: (1) How accurate is preoperative biopsy in determining whether a peripheral cartilage tumor of the pelvis is benign or malignant? (2) Is the thickness of the cartilage cap as determined by MRI associated with the likelihood that a given peripheral cartilage tumor is malignant? (3) What is local recurrence-free survival (LRFS), metastasis-free survival (MFS), and disease-specific survival (DSS) in peripheral chondrosarcoma of the pelvis and is it associated with surgical margin? METHODS: Between 2005 and 2022, 289 patients had diagnoses of peripheral cartilage tumors of the pelvis (either pedunculated or sessile) and were treated at one tertiary sarcoma center (the Royal Orthopaedic Hospital, Birmingham, UK). These patients were identified retrospectively from a longitudinally maintained institutional database. Those whose tumors were asymptomatic and discovered incidentally and had cartilage caps ≤ 1.5 cm were discharged (95 patients), leaving 194 patients with tumors that were either symptomatic or had cartilage caps > 1.5 cm. Tumors that were asymptomatic and had a cartilage cap > 1.5 cm were followed with MRIs for 2 years and discharged without biopsy if the tumors did not grow or change in appearance (15 patients). Patients with symptomatic tumors that had cartilage caps ≤ 1.5 cm underwent removal without biopsy (63 patients). A total of 82 patients (63 with caps ≤ 1.5 cm and 19 with caps > 1.5 cm, whose treatment deviated from the routine at the time) had their tumors removed without biopsy. This left 97 patients who underwent biopsy before removal of peripheral cartilage tumors of the pelvis, and this was the group we used to answer research question 1. The thickness of the cartilage cap was recorded from MRI and measuring to the nearest millimeter, with measurements taken perpendicular in the plane that best allowed the greatest measurement. Patient survival rates were assessed using the Kaplan-Meier method with 95% confidence intervals as median observation times to estimate MFS, LRFS, and DSS. RESULTS: Of malignant tumors biopsied, in 49% (40 of 82), the biopsy result was recorded as benign (or was considered uncertain regarding malignancy). A malignant diagnosis was correctly reported in biopsy reports in 51% (42 of 82) of patients, and if biopsy samples with uncertainty regarding malignancy were excluded, the biopsy identified a lesion as being malignant in 84% (42 of 50) of patients. The biopsy results correlated with the final histologic grade as recorded from the resected specimen in only 33% (27 of 82) of patients. Among these 82 patients, 15 biopsies underestimated the final histologic grade. The median cartilage cap thickness for all benign osteochondromas was 0.5 cm (range 0.1 to 4.0 cm), and the median cartilage cap thickness for malignant peripheral chondrosarcomas was 8.0 cm (range 3.0 to 19 cm, difference of medians 7.5 cm; p < 0.01). LRFS was 49% (95% CI 35% to 63%) at 3 years for patients with malignant peripheral tumors with < 1-mm margins, and LRFS was 97% (95% CI 92% to 100%) for patients with malignant peripheral tumors with ≥ 1-mm margins (p < 0.01). DSS was 100% at 3 years for Grade 1 chondrosarcomas, 94% (95% CI 86% to 100%) at 3 years for Grade 2 chondrosarcomas, 73% (95% CI 47% to 99%) at 3 and 5 years for Grade 3 chondrosarcomas, and 20% (95% CI 0% to 55%) at 3 and 5 years for dedifferentiated chondrosarcomas (p < 0.01). DSS was 87% (95% CI 78% to 96%) at 3 years for patients with malignant peripheral tumors with < 1-mm margin, and DSS was 100% at 3 years for patients with malignant peripheral tumors with ≥ 1-mm margins (p = 0.01). CONCLUSION: A thin cartilage cap (< 3 cm) is characteristic of benign osteochondroma. The likelihood of a cartilage tumor being malignant increases after the cartilage cap thickness exceeds 3 cm. In our experience, preoperative biopsy results were not reliably associated with the final histologic grade or malignancy, being accurate in only 33% of patients. We therefore recommend observation for 2 years for patients with pelvic osteochondromas in which the cap thickness is < 1.5 cm and there is no associated pain. For patients with tumors in which the cap thickness is 1.5 to 3 cm, we recommend either close observation for 2 years or resection, depending on the treating physician's decision. We recommend excision in patients whose pelvic osteochondromas show an increase in thickness or pain, preferably before the cartilage cap thickness is 3 cm. We propose that surgical resection of peripheral cartilage tumors in which the cartilage cap exceeds 3 cm (aiming for clear margins) is reasonable without preoperative biopsy; the role of preoperative biopsy is less helpful because radiologic measurement of the cartilage cap thickness appears to be accurately associated with malignancy. Biopsy might be helpful in patients in whom there is diagnostic uncertainty or when confirming the necessity of extensive surgical procedures. Future studies should evaluate other preoperative tumor qualities in differentiating malignant peripheral cartilage tumors from benign tumors. LEVEL OF EVIDENCE: Level III, diagnostic study.

The Importance of Awaiting Biopsy Results in Solitary Pathological Proximal Femoral Fractures : Do We Need to Biopsy Solitary Pathological Fractures?

BACKGROUND: The optimal surgical treatment for patients presenting with (impending and complete) pathological proximal femoral fractures is predicated on prognosis. Guidelines recommend a preoperative biopsy to exclude sarcomas, however no evidence confirms a benefit. OBJECTIVE: This study aimed to describe the diagnostic accuracy, morbidity and sarcoma incidence of biopsy results in these patients. MATERIAL AND METHODS: All patients (n = 153) presenting with pathological proximal femoral fractures between 2000 and 2019 were retrospectively evaluated. Patients after inadvertent surgery (n = 25) were excluded. Descriptive statistics were used to evaluate the accuracy and morbidity of diagnostic biopsies. RESULTS: Of 112/128 patients who underwent biopsy, nine (8%) biopsies were unreliable either due to being inconclusive (n = 5) or because the diagnosis changed after resection (n = 4). Of impending fractures, 32% fractured following needle core biopsy. Median time from diagnosis to surgery was 30 days (interquartile range 21-46). The overall biopsy positive predictive value (PPV) to differentiate between sarcoma and non-sarcoma was 1.00 (95% confidence interval [CI] 0.88-1.00). In patients with a previous malignancy (n = 24), biopsy (n = 23) identified the diagnosis in 83% (PPV 0.91, 95% CI 0.71-0.99), of whom five (24%) patients had a new diagnosis. In patients without a history of cancer (n = 61), final diagnosis included carcinomas (n = 24, 39.3%), sarcomas (n = 24, 39.3%), or hematological malignancies (n = 13, 21.3%). Biopsy (n = 58) correctly identified the diagnosis in 66% of patients (PPV 0.80, 95% CI 0.67-0.90). CONCLUSION: This study confirms the importance of a preoperative biopsy in solitary pathological proximal femoral fractures due to the risk of sarcoma in patients with and without a history of cancer. However, biopsy delays the time to definite surgery, results can be inconclusive or false, and it risks completion of impending fractures.

Early radiographic osseointegration of a novel highly porous 3D-printed titanium collar for megaprostheses compared to a previous generation smooth HA-coated collar.

PURPOSE: Extracortical osseointegration at the collar-bone interface of megaprostheses is associated with improved implant stability, lower rates of stem fracture and loosening. The use of hydroxy-apatite (HA-) coated collars showed mixed results in previously published reports. A novel collar system has recently become available utilizing additive manufacturing technology to create a highly porous titanium collar with a calcium-phosphate coated surface. The aim of this study was to evaluate our early experience with this novel collar and compare it to the previously used HA-coated model. METHODS: Twenty patients who underwent megaprostheses implantation utilizing the novel collar system were case matched to 20 patients who had previously undergone a HA-coated collar. A minimum radiological follow-up of three months was available in all included patients. Osseointegration was evaluated using postoperative plain radiographs in two planes based on a previously published semi-quantitative score. RESULTS: Compared to the HA-coated collar the use of the novel highly porous collar was associated with a higher proportion of cases demonstrating osseointegration at the bone-collar interface (80% vs. 65%). Application of the highly porous collar led to a significantly shortened time to reach the final ongrowth score (173 ± 89 days vs. 299 ± 165 days, p < 0.05). At one year follow-up, 90% of the novel collars had reached their final osseoingration grade compared to 50% in the HA-coated collar group (p < 0.001). Radiological osseointegration was seen in 71% for highly porous collars where the indication was revision arthroplasty, compared to 27% in reported in the literature. CONCLUSION: These results indicate more reliable and accelerated osseointegration at the bone-collar interface of a novel highly porous collar system compared to a previously used HA-coated collar. Further studies are warranted to confirm these findings.

Anatomical distribution, the incidence of malignancy and diagnostic workup in the pathological lesions of the clavicle: a review of 410 cases.

BACKGROUND: The clavicle poses a diagnostic dilemma of the pathological lesions due to the wide range of pathologies seen at this site. This study aimed to identify and stratify various pathologies seen in the clavicle and to guide ways of investigation for diagnosis based on age, site and investigation findings. MATERIALS AND METHODS: Four hundred and ten cases with clavicle lesions were identified in our database. Data were collected about the patient's medical history, previous investigation, inflammatory markers radiological investigations and biopsy. All patients were worked up and managed after discussion in a multidisciplinary team meeting (MDT). RESULTS: Non-malignant lesions accounted for 79% of cases. Infection was the most common diagnosis (39%) and the commonest diagnosis in those less than 20 years of age. 73% of the lesions were found at the medial end of the clavicle. Malignant tumours were 21%, while primary benign bone tumours accounted for only 14%. 50% of the malignant lesions were due to metastatic disease. The risk of malignancy increases with advancing age. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were not sensitive as a diagnostic tool in cases of osteomyelitis confirmed by histology. Magnetic resonance imaging (MRI) was noted to have high sensitivity and specificity for identifying the nature of a lesion and diagnosis. CONCLUSION: We have identified age as a positive predictor of a malignant cause in pathological lesions of the clavicle. MRI should be considered in all these cases. CRP and ESR have poor predictive values in diagnosing infection in the clavicle. Patients presenting with clavicle lesions should be discussed in a specialist MDT and undergo a systemic diagnostic workup, still in some cases, diagnosis can be speculated based on the patient's age, location of the lesion within the clavicle and the features seen on the MRI scan. LEVEL OF EVIDENCE: IV.

Repeat revision TKR for failed management of peri-prosthetic infection has long-term success but often require multiple operations: a case control study.

BACKGROUND: Prosthetic joint infection (PJI) is associated with poor outcomes and catastrophic complications. The aim of this study was to present the outcomes of re-revision surgery for PJI of the knee following previous failed two-stage exchange arthroplasty. MATERIALS AND METHODS: A retrospective analysis was performed of 32 patients who underwent re-revision knee arthroplasty, having already undergone at least one previous two-stage exchange for PJI with a minimum follow-up of two-years for alive patients. Outcomes were compared to a matched control of two-stage revisions for PJI of a primary knee replacement also containing 32 patients. Outcomes investigated were eradication of infection, re-operation, mortality and limb-salvage rate. RESULTS: Successful eradication of infection was achieved in 50% of patients following re-revision surgery, compared with 91% following two-stage exchange of primary knee replacement for PJI (p < 0.001). Fourteen (44%) patients required further re-operation compared with three (9%) patients in the primary group (p = 0.006). Amputation was performed in one case (3%) with thirteen patients (92%) who had infection controlled by debridement, antibiotics and implant retention (DAIR), further revision surgery or arthrodesis. Two patients died with infection (6%) and the long-term rate for infection control was 91%. The mean number of procedures following surgery for the re-revision group was 2.8 (0-9) compared with 0.13 (0-1) for the primary two-stage group (p < 0.001). Five-year patient survival was 90.6% (95% CI 77.1-100). The limb-salvage rate for the re-revision cohort was 97%. CONCLUSION: Outcomes for re-revision knee arthroplasty for PJI have higher re-operation and failure rates, but no worse mortality than in revisions of primary knee replacements. Failures can successfully be managed by further operation.

Membrane-type 1 matrix metalloproteinase as predictor of survival and candidate therapeutic target in Ewing sarcoma.

BACKGROUND: Ewing sarcoma (ES) is the second most common primary bone malignancy, with an urgent need for new treatments. ES is associated with high rates of progression and relapse, driven by drug-resistant cells capable of migration, self-renewal and single-cell tumorigenesis, termed cancer stem-like cells (CSCs). Membrane-type 1 matrix metalloproteinase (MT1-MMP) is a membrane-bound proteolytic enzyme, which, via direct and indirect mechanisms, digests four of the main types of collagen. This can be hijacked in malignancy for invasion and metastasis, with high expression predicting decreased survival in multiple cancers. In this study, we have examined the hypothesis that MT1-MMP is expressed by ES cells and explored the relationship between expression and outcomes. PROCEDURE: MT1-MMP expression in ES established cell lines, primary patient-derived cultures and daughter ES-CSCs was characterised by RNA sequencing, Western blotting, immunocytochemistry and flow cytometry. Immunohistochemistry was used to detect MT1-MMP in tumour biopsies, and the relationship between expression, event-free and overall survival examined. RESULTS: MT1-MMP was detected at both RNA and protein levels in five of six established cell lines, all primary cultures (n = 25) and all daughter ES-CSCs (n = 7). Immunohistochemistry of treatment-naïve biopsy tissue demonstrated that high MT1-MMP expression predicted decreased event-free and overall survival (p = .017 and .036, respectively; n = 47); this was not significant in multivariate analysis. CONCLUSIONS: MT1-MMP is expressed by ES cells, including ES-CSCs, making it a candidate therapeutic target. The level of MT1-MMP expression at diagnosis may be considered as a prognostic biomarker if validated by retrospective analysis of a larger cohort of clinical trial samples.

Pelvic reconstruction using an ice-cream cone prosthesis: correlation between the inserted length of the coned stem and surgical outcome.

BACKGROUND: Acetabular reconstruction using an ice-cream cone prosthesis has been a reliable reconstruction option following pelvic tumour resection. However, it remains unknown which factor determines the success of this procedure. We aimed to determine risk factors for complications and functional loss in acetabular reconstruction using an ice-cream cone prosthesis. PATIENTS AND METHODS: Fifty-four patients with malignant bone tumours who underwent acetabular reconstruction using an ice-cream cone prosthesis between 2004 and 2016 were studied. The bone-stem ratio was calculated as the ratio of the inserted length into the bone per the entire stem length. RESULTS: A total of 26 (48%) patients had at least one complication and 11 patients (20%) required surgical interventions. The complication rates were 71% and 40% with a bone-stem ratio ≤ 50% and > 50%, respectively (p = 0.026), and the bone-stem ratio significantly stratified the risk of complications (≤ 50%: OR, 4.67 versus > 50%; p = 0.048). The mean MSTS score at the final follow-up was 60% (range 23-97%): the scores were significantly lower in patients with complications/leg-length discrepancy (52%) than in those without (79%; p = 0.002). The mean score with a bone-stem ratio ≤ 50% was significantly lower than the score with a ratio > 50%, especially in patients who underwent non-navigated reconstructions (33% versus 64%; p = 0.001). CONCLUSION: The inserted length of the coned stem into residual bone was predictive of complications and functional outcome. Surgical indication for this procedure should be considered with the size of the remaining ilium to stabilise the prosthesis with a coned stem longer than half length.

Surgical treatment of skeletal metastases in proximal tibia: a multicenter case series of 74 patients.

Background and purpose - The proximal tibia is a rare site for metastatic bone disease and is a challenging anatomical site to manage due to the proximity to the knee joint and poor soft tissue envelope. We investigated implant survival and complications of different surgical strategies in the treatment of proximal tibia pathological fractures.Patients and methods - The study comprised a 4 medical center, retrospective analysis of 74 patients surgically treated for metastases of the proximal tibia. Patient records were reviewed to identify outcome, incidence, and type of complications as well as contributing factors.Results - Reconstruction techniques comprised cement-augmented osteosynthesis (n = 33), tumor prosthesis (n = 31), and total knee arthroplasty with long cemented stems (n = 10). Overall implant survival was 88% at 6 months and 1 year, and 67% at 3 years. After stratification by technique, the implant survival was 82% and 71% at 1 and 3 years with tumor prosthesis, 100% at 1 and 3 years with total knee arthroplasty, and 91% at 1 year and 47% at 3 years with osteosynthesis. Preoperative radiotherapy decreased implant survival. Complications were observed in 19/74 patients. Treatment complications led to amputation in 5 patients.Interpretation - In this study, the best results were seen with both types of prothesis reconstructions, with good implant survival, when compared with treatment with osteosynthesis. However, patients treated with tumor prosthesis showed an increased incidence of postoperative infection, which resulted in poor implant survival. Osteosynthesis with cement is a good alternative for patients with short expected survival whereas endoprosthetic replacement achieved good medium-term results.

Extra-articular resection for bone sarcomas involving the hip joint.

AIM: The aim of this study was to determine the oncologic, functional, and clinical outcomes after the extra-articular resection and limb-salvage reconstruction of the hip joint. METHODS: A retrospective study of 34 patients who underwent extra-articular resection of the hip joint for bone sarcomas between 1996 and 2016 was conducted. The primary tumor site was pelvis in 26 patients (76%) and femur in eight (24%). RESULTS: The surgical margins achieved were clear in 31 (91%) patients, and seven (21%) patients developed local recurrence; mostly occurring in pelvic tumors (n = 6). The 3-year overall survival was 63% with a median follow-up of 38 months (range, 5-219), which showed no statistical difference in tumor location. The most common complication was deep infection (n = 7) and dislocation (n = 7), mostly seen in pelvic tumors. Implant failure was seen in two patients with pelvic tumors, while no failure was noted in patients with femoral tumors. The median Musculoskeletal Tumour Society score was 69%; 67% for pelvic tumors and 73% for femoral tumors (P = .535). CONCLUSION: Despite complex surgery, extra-articular resection of the hip joint can achieve oncologically and functionally acceptable outcomes. While tumors of the pelvis are associated with a higher incidence of infection and local recurrence after resection, resection of tumors involving the femur are well tolerated.

Mortality of high-risk orthopaedic oncology patients during the COVID-19 pandemic: A prospective cohort study.

BACKGROUND AND OBJECTIVES: Should the threshold for orthopaedic oncology surgery during the coronavirus disease-2019 (COVID-19) pandemic be higher, particularly in men aged 70 years and older? This study reports the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during, respiratory complications and 30-day mortality during the COVID-19 pandemic. METHODS: This prospective observational cohort study included 100 consecutive patients. The primary outcome measure was 14-day symptoms and/or SARS-CoV-2 test. The secondary outcome was 30-day postoperative mortality. RESULTS: A total of 100 patients comprising 35 females and 65 males, with a mean age of 52.4 years (range, 16-94 years) included 16 males aged greater than 70 years. The 51% of patients were tested during their admission for SARS-CoV-2; 5% were diagnosed/developed symptoms of SARS-CoV-2 during and until 14 days post-discharge; four were male and one female, mean age 41.2 years (range, 17-75 years), all had primary malignant bone or soft-tissue tumours, four of five had received immunosuppressive therapy pre-operatively. The 30-day mortality was 1% overall and 20% in those with SARS-CoV-2. The pulmonary complication rate was 3% overall. CONCLUSIONS: With appropriate peri-operative measures to prevent viral transmission, major surgery for urgent orthopaedic oncology patients can continue during the COVID-19 pandemic. These results need validating with national data to confirm these conclusions.

Acetabular reconstruction with an ice-cream cone prosthesis following resection of pelvic tumors: Does computer navigation improve surgical outcome?

BACKGROUND AND OBJECTIVES: Acetabular reconstruction with a coned-stem prosthesis has been one of the reliable procedures following pelvic tumor resections but is associated with a risk of complications and postoperative morbidity. We investigated whether navigated reconstruction could decrease the complication rate and optimize outcomes. METHODS: A retrospective study was conducted on 33 patients who underwent acetabular resection and reconstruction with ice-cream cone prostheses; outcomes were compared between the navigated and nonnavigated groups. RESULTS: A clear margin was obtained in 91% and 82% of the navigated and nonnavigated groups, respectively. The local recurrence (LR) rate was 12%, and all LRs occurred in the nonnavigated group. The rate of major complications requiring surgical intervention was significantly lower in the navigated group (9%) than in the nonnavigated group (50%; P = .024). Two implant failures occurred in the nonnavigated group. Functional outcomes were significantly correlated with the occurrence of major complications (P = .010) and the use of navigation (P = .043); superior functional scores were observed in the navigated group (Musculoskeletal Tumor Society, 73% vs 55%; Toronto Extremity Salvage Score, 73% vs 56%). CONCLUSION: Ice-cream cone prosthesis is an acceptable reconstruction modality following periacetabular tumor resections, and computer navigation are useful to facilitate proper resection margins and implant position.

Is Microscopic Vascular Invasion in Tumor Specimens Associated with Worse Prognosis in Patients with High-grade Localized Osteosarcoma?

BACKGROUND: Other than metastases at diagnosis and histological response to preoperative chemotherapy, there are few reliable predictors of survival in patients with osteosarcoma. Microscopic vascular invasion (MVI) has been identified in the resection specimens of patients with osteosarcoma. However, it is unknown whether the MVI in resected specimens is associated with worse overall survival and higher cumulative incidence of local recurrence or metastasis in a large cohort of patients younger than 40 years with high-grade localized osteosarcoma. QUESTIONS/PURPOSES: (1) Is MVI associated with worse overall survival and higher cumulative incidence of events (local recurrence or metastasis) in patients younger than 40 years with high-grade localized osteosarcoma? (2) What clinical characteristics are associated with MVI in patients with high-grade localized osteosarcoma? METHODS: A total of 625 patients younger than 40 years with primary high-grade osteosarcoma between 1997 and 2016 were identified in our oncology database. We included patients younger than 40 years with primary high-grade osteosarcoma who underwent definitive surgery and preoperative and postoperative chemotherapy. The minimum follow-up period was 2 years after treatment. Patients with the following were excluded: metastasis at initial presentation (21%, n = 133), progression with preoperative chemotherapy precluding definitive surgery (6%, n = 38), surgery at another unit (2%, n = 13), lost to follow-up before 2 years but not known to have died (3%, n = 18), and death related to complications of preoperative chemotherapy (1%, n = 4). A retrospective pathologic and record review was conducted in the remaining 419 patients. The median follow-up period was 5 years (interquartile range [IQR] 3 to 9 years). The overall survival of the entire group (n = 419) was 67% [95% CI 63 to 72] at 5 years. Of the 419 patients, 10% (41) had MVI in their resection specimens. The Kaplan-Meier method was used to estimate overall survival. The cumulative incidence of events captured the first event of either metastasis or local recurrence. This analysis was completed with a competing risk framework: deaths without evidence of local recurrence or metastasis were regarded as a competing event. Clinical and histological variables (sex, age, tumor site, tumor largest dimension, surgical margin, chemotherapy-induced necrosis, type of surgery, histologic type of tumor, type of chemotherapy regimen, pathologic fracture, and MVI) were evaluated using the log-rank test or Gray test in the univariate analyses and Cox proportional hazard model or Fine and Gray model in the multivariate analyses. RESULTS: After adjusting for other factors, multivariate analyses showed that the presence of MVI in resection specimens was associated with worse overall survival and higher cumulative incidence of event (hazard ratio 1.88 [95% CI 1.22 to 2.89]; p = 0.004 and HR 2.33 [95% CI 1.56 to 3.49]; p < 0.001, respectively). A subgroup analysis demonstrated that the relationship between MVI and survival applied only to patients with a poor response to chemotherapy (less than 90% necrosis; overall survival at 5 years, MVI [+] = 24% [95% CI 11 to 39] versus MVI [-] = 60% [95% CI 52 to 66]; p < 0.001 and cumulative incidence of events at 5 years, MVI [+] = 86% [95% CI 68 to 94] versus MVI [-] = 54% [95% CI 46 to 61]; p < 0.001). The MVI (+) group had a higher proportion of patients with a poor response to chemotherapy (85% [35 of 41] versus 53% [201 of 378]; p < 0.001), involved margins (15% [6 of 41] versus 5% [18 of 378]; p = 0.021), and limb-ablative surgery (37% [15 of 41] versus 21% [79 of 378]; p = 0.022) than the MVI (-) group did. CONCLUSIONS: MVI is associated with lower overall survival and higher cumulative incidence of local recurrence or metastasis, especially in patients with a poor histologic response to preoperative chemotherapy. Future studies in patients treated for osteosarcoma should consider this observation when planning new trials. LEVEL OF EVIDENCE: Level III, therapeutic study.

Denosumab in giant cell tumour of bone in the pelvis and sacrum: Long-term therapy or bone resection?

INTRODUCTION: Surgery of GCTB in sacrum and pelvis is challenging, with high rates of complications and local recurrence. Denosumab can consolidate the peripheral rim of the tumour, thus reducing the rate of morbidities of surgery. The aim of this paper is to evaluate the use of denosumab in pelvic/sacrum giant cell tumours of bone (GCTB). PATIENTS AND METHODS: We retrospectively reviewed a cohort of 26 patients with aggressive GCTB in sacrum or pelvis treated with denosumab at two referral centres. Clinical response and local recurrence were recorded and the radiologic responses were evaluated with the MDA criteria. RESULTS: 69% of the pelvic GCTB treated with denosumab presented partial or good radiologic responses (type 2A or 2B) after 49 weeks of treatment. Denosumab was administered as adjuvant therapy prior and after surgery in 11 patients (group A), and as the only treatment in 15 patients (group B). In group A, 62% of local recurrence was observed in patients treated with intralesional curettage. No recurrences were identified after en bloc resection. In group B, 9 patients were on continuous bimonthly long term denosumab administration with type 2A and 2B responses. Six patients stopped denosumab and 66% remained stable after 10 months of follow-up. CONCLUSIONS: Long-term denosumab therapy can be considered with curative intent for pelvic and sacrum GCTB. If surgical intervention is required wide resection may be advisable to reduce the risk of recurrence.

Sacral chordoma: do the width of surgical margin and the use of photon/proton radiotherapy affect local disease control?

PURPOSE: Chordoma is a rare but highly aggressive primary bone sarcoma that arises commonly from the sacrum. While en bloc resection has been the mainstay of the treatment, the role of resection margin in millimetres with/without adjuvant radiotherapy (RT) has been unknown. We investigated the prognostic impact of surgical margin width, adjuvant RT, and their combined factor for sacral chordoma. METHODS: Forty-eight patients who underwent surgical treatment between 1996 and 2016 were studied. Of these, 11 patients (23%) received adjuvant RT; photon RT in 7 (15%) and proton RT in 4 (8%). Margins were microscopically measured in millimetres from the resection surface to the closest tumour on histologic slides. RESULTS: The five year and ten year disease-specific survival was 88% and 58%, respectively, and the local recurrence (LR) rate was 48%. The LR rate with 0-mm, < 1.5-mm, and ≥ 1.5-mm margin was 50% (group 1), 50% (group 2: RT-, 61%; group 3: RT+, 14%), and 0% (group 4), respectively. We observed a significantly lower LR rate in patients with adjuvant photon/proton RT (18%) than without it (57%; p = 0.026), and no LR was observed after post-operative proton RT. The combined factor of margin with RT clearly stratified the LR risk: patients of group 1 (positive margin) and 2 (< 1.5-mm margin, RT-) had approximately 7.5× LR risk (p = 0.049) compared with those of group 3 (< 1.5-mm margin, RT+) and 4 (≥ 1.5-mm margin). CONCLUSION: This study identified the lowest risk of local failure in tumour resection with ≥ 1.5-mm margin or negative but < 1.5-mm margin with the use of adjuvant photon/proton radiotherapy for sacral chordoma. Early results of adjuvant proton RT demonstrated excellent local control.

Localized synovial sarcoma: A single institutional study of 191 patients with a minimum follow-up of 5 years for survivors.

PURPOSE: Factors affecting long-term outcomes of synovial sarcoma (SS) remain unknown. Here, we aimed to investigate the long-term oncological outcomes and prognostic factors in a large group of patients with surgically-treated localized SS. PATIENTS AND METHODS: Between 1980 and 2011, 191 patients (94 males and 97 females) were treated at a single hospital with a minimum follow-up of 5 years for survivors. The median age was 35 years (range, 3-80 years), and the median follow-up period was 83 months (range, 3-235 months). RESULTS: Disease-specific survival was 76.4% and 60.4% at 5 and 10 years, respectively. Local recurrence occurred in 23 patients at a median of 33 months (range, 6-158 months), and metastasis occurred in 73 patients at a median of 20 months (range, 2-166 months). In multivariate analysis, grade 3 tumors sized ≥5 cm were significantly associated with worse survival. Ten patients (5.2%) developed metastasis more than 5 years after surgery. CONCLUSION: Tumor size and grade govern prognosis in surgically-treated localized SS in long-term settings. If adequately treated patients have not developed metastases for 5 years after surgery, the risk of subsequently developing metastases was lower than previously reported.

Surgical treatment for pelvic Ewing sarcoma: What is a safe and functional acetabular reconstruction when combined with modern multidisciplinary treatments?

PURPOSE: The purpose of this study was to clarify which local treatment is oncologically and functionally effective in pelvic Ewing sarcoma (ES). METHODS: A consecutive series of patients who underwent pelvic resections and acetabular reconstructions after chemotherapy between 1986 and 2016 at a supra-regional center were evaluated. RESULTS: The cohort consisted of 35 patients. The 5-year overall survival (OS) and local recurrence-free survival (LRFS) was 61% and 72%, respectively. Preoperative radiotherapy (RT) and surgery provided an excellent/good histological response in 92% and achieved significantly better OS (5 years, 64%) and LRFS (5 years, 100%) than surgery alone or surgery with postoperative RT. The Musculoskeletal Tumor Society functional scores were significantly better in patients with hip transposition than those with structural reconstructions (74% vs 57%; P = .031) using custom-made prostheses, irradiated autografts, and ice-cream cone prostheses. These scores were significantly lower if patients had deep infection (P = .035), which was the most common complication (28%) in structural reconstructions but did not occur in hip transposition even when performed after preoperative RT. CONCLUSION: Acetabular reconstruction with hip transposition resulted in no deep infection and superior function in patients with pelvic ES even when combined with preoperative RT, which improved tumor necrosis and rate of local control and survival.

Is the Width of a Surgical Margin Associated with the Outcome of Disease in Patients with Peripheral Chondrosarcoma of the Pelvis? A Multicenter Study.

BACKGROUND: We attempted to resect peripheral chondrosarcoma of the pelvis with clear margins. Because of the proximity of vessels or organs, there is still concern that narrow surgical margins may have an adverse effect on disease outcomes. Although current guidelines recommend resection of histologic Grade II or Grade III chondrosarcomas with a "wide" margin, there are no specific recommendations for the adequate width of a surgical margin. QUESTIONS/PURPOSES: (1) What is the disease-specific and local recurrence-free survival of patients with peripheral chondrosarcoma of the pelvis treated with resection or amputation? (2) Is the width of a surgical margin associated with the outcome of disease in patients with peripheral chondrosarcoma of the pelvis? (3) Does the histologic grade as determined with a preoperative biopsy correlate with the final grade after resection? (4) What are surgical complications in these patients? METHODS: We retrospectively reviewed records from three international collaborating hospitals. Between 1983 and 2017, we resected 262 pelvic chondrosarcomas of all types. After reviewing the pathologic reports of these patients, we included 52 patients with peripheral chondrosarcomas of the pelvis who had an osteochondroma-like lesion at the base of the tumor and a cartilage cap with malignant cells in resected specimens. To be eligible for this study, a patient had to have a minimum of 1 year of follow-up. Two patients were excluded because they had less than 1 year of follow-up, leaving 50 patients for inclusion in this study. The median follow-up duration was 7.0 years (interquartile range 2.1-10 years). The median age was 37 years (IQR 29-54 years). The ilium was the most frequently affected bone (in 36 of 50 patients; 72%). The histologic status of the surgical margin was defined as microscopically positive (0 mm), negative < 1 mm, or negative ≥ 1 mm. Thirteen of the 50 patients (26%) had local recurrence. Seven of 34 patients had Grade I tumors, five of 13 had Grade II tumors, and one of three had a Grade III tumor. Nine of 16 patients had multiple local recurrences. Two patients with Grade I tumors and two with Grade II tumors died because of pressure effects caused by local recurrence. RESULTS: The 10-year disease-specific and local recurrence-free survival rates were 90% (95% confidence interval, 70-97) and 69% (95% CI, 52-81), respectively. A surgical margin ≥ 1 mm (n = 16) was associated with a better local recurrence-free survival rate than a surgical margin < 1 mm (n = 17) or 0 mm (n = 11) (10-year local recurrence-free survival: resection margin ≥ 1 mm = 100% versus < 1 mm = 52% [95% CI, 31 to 70]; p = 0.008). No patients with a surgical margin ≥ 1 mm had local recurrence, metastasis, or disease-related death, irrespective of tumor grade. Patients with local recurrence (n = 13) showed worse disease-specific survival than those without local recurrence (n = 37) (10-year disease-specific survival: local recurrence [+] = 59% [95% CI, 16 to 86] versus local recurrence [-] = 100%; p=0.001]). The preoperative biopsy results correctly determined the tumor grade in 15 of 41 patients (37%). The most frequent complication after surgery was local recurrence (13 of 50 patients, 26%). Deep infection was the most frequent nononcologic complication (four patients). CONCLUSIONS: We found a high local recurrence rate after surgical treatment of a peripheral pelvic chondrosarcoma, which was related to the width of the surgical margin. These local recurrences led to inoperable recurrent tumors and death. The tumor grade as determined by preoperative biopsy was inaccurate in 2/3 of patients compared with the final histologic assessment. Therefore, we believe every attempt should be made to achieve a negative margin during the initial resection to lessen the likelihood of local recurrence of peripheral chondrosarcoma of the pelvis of all grades. A margin of 1 mm or more appeared to be sufficient in these patients. LEVEL OF EVIDENCE: Level III, therapeutic study.

Frank Stinchfield Award: Identification of the At-risk Genotype for Development of Pseudotumors Around Metal-on-metal THAs.

BACKGROUND: Once touted as the future of hip arthroplasty, metal-on-metal (MoM) bearing surfaces have fallen sharply from favor with the emergence of a strong body of evidence demonstrating unacceptably high premature implant failure rates. The previously unpredictable development of adverse local tissue reactions (ALTRs) has been a substantive contributor to this. Although the underlying pathophysiology of these so-called "pseudotumors" is now well understood, the fundamental predisposing patient risk factors have remained elusive. QUESTIONS/PURPOSES: The aim of this research, as a clinical-genotype correlation analysis, was to identify specific alleles (genes) associated with the development of ALTRs in patients with in situ MoM THAs. METHODS: A case-control study of patients who received a large-head, primary MoM THA between 2005 and 2008 was performed with a minimum followup of 5 years. Twenty-six patients who had undergone revision of a primary MoM THA secondary to symptomatic ALTRs were recruited. The mean timeframe from primary MoM THA to symptomatic revision was 5.5 years (range, 1-10 years). Twenty-eight control subjects were randomly selected asymptomatic patients with no evidence of ALTRs on protocol-specific screening. Baseline demographics and high-resolution genotype (human leukocyte antigen [HLA] Class II) were collected for all patients. Cohorts were similar with respect to age at the time of primary MoM THA (mean, 54.8 versus 54.9 years, p = 0.95) and serum cobalt (mean, 5.5 versus 8.5 µg/L, p = 0.09) and chromium concentrations (mean, 2.9 versus 4.2 µg/L, p = 0.27). The association between genotype and revision surgery secondary to ALTRs was determined with gender as a covariate. RESULTS: The prevalence of the risk genotype was 30% (16 of 54) among the entire cohort. Adjusting for sex, the odds of revision were 6.1 times greater among patients with the risk genotype present than among patients without (95% confidence interval [CI], 1.5-25.4; p = 0.01). Among females, the specificity of the risk genotype was 1.0 (95% CIexact, 0.5-1.0; pexact = 0.03), and for males, it was 0.8 (95% CIexact, 0.6-0.9; pexact < 0.01). CONCLUSIONS: The findings of this study suggest that, among patients with a primary MoM THA, allelic variation within the HLA Class II loci may be a strong, independent risk factor associated with the need for subsequent revision surgery secondary to pseudotumor formation. CLINICAL RELEVANCE: Given the hypothesis-generating nature of this novel undertaking, confirmatory prospective clinical studies are required to further elucidate this correlation and to explore the clinical utility of targeted genetic screening in this specific population. This research may, however, represent a key missing piece in the puzzle that is metal ion-induced pseudotumor formation.

Outcome of Pelvic Bone Sarcomas in Children.

BACKGROUND: Malignant bone tumors of the pelvis in children are rare and knowledge of their behavior is limited. METHODS: A total of 113 skeletally immature patients under 16 years of age, comprising 58 females and 55 males were treated between 1983 and 2014. Tumors comprised Ewing's sarcoma (ES) in 88 (77.9%) or osteosarcoma (OS) in 25 (22.1%). Metastases at diagnosis were present in 36 (31.9%). The mean follow-up was 5.2 years (2 to 16). RESULTS: For patients with ES, the overall survival was 37.1% at 5-years and 33.5% at 10-years and 31.7% at 5- and 10-years in patients with OS. Local recurrence occurred in 24 patients with ES (27.3%) and 7 patients with OS (43.7%). Chemotherapy response was a predictor of local recurrence in ES with the lowest incidence seen in those with a good response to chemotherapy treated with a combination of radiotherapy and surgery. In patients with OS, both surgical margin and chemotherapy response influenced local control. CONCLUSIONS: Attaining a wide surgical margin should be the aim of treatment for all children with primary bone tumors of the pelvis. In ES, chemotherapy response has a greater influence on disease free and overall survival. Patients who demonstrate a poor response to chemotherapy should be considered for subsequent radiotherapy. Effort should be directed toward identifying nonhistologic methods of assessing chemotherapy response. LEVEL OF EVIDENCE: Level IV-retrospective case study.