Can low-grade chondrosarcoma in flat bones be treated with intralesional curettage and cryotherapy?

BACKGROUND AND OBJECTIVES: Chondrosarcomas in flat bones are thought to be more aggressive in their behavior, and little is known about intralesional treatment outcomes of low-grade chondrosarcoma in these locations. We tried to find the differences between patients who had low-grade chondrosarcoma in their flat bones versus those with long bone involvement with regard to (1) disease outcome, (2) functional outcome, and (3) treatment complications. METHODS: We retrospectively reviewed 44 patients with primary low-grade chondrosarcoma who were treated with intralesional curettage and cryotherapy. The patients were divided by location of tumor, group I (flat bones, seven patients) and group II (long bones, 37 patients). RESULTS: The local recurrence rate was higher in group I with 5 years disease-free survival of 80.0% in group I and 97.0% in group II (p = 0.001). All recurrent cases were noted to have initially presented with soft tissue extension (Enneking stage IB). The mean Musculoskeletal Tumor Society score at the last follow-up was 21.7 in group I and 27.9 in group II (p = 0.045). CONCLUSIONS: Intralesional curettage and cryotherapy for low-grade chondrosarcoma appear to be a safe and reasonable surgical option for patients with lesions confined to bone (Enneking stage IA). LEVEL OF EVIDENCE: Level III, retrospective cohort study. See the Guidelines for Authors for a complete description of levels of evidence.

Denosumab in patients with giant-cell tumour of bone: a multicentre, open-label, phase 2 study.

BACKGROUND: Giant-cell tumour of bone (GCTB) is a rare, locally aggressive osteoclastogenic stromal tumour of the bone. This phase 2 study aimed to assess the safety and activity of denosumab in patients with surgically salvageable or unsalvageable GCTB. METHODS: In this multicentre, open-label, phase 2 study done at 30 sites in 12 countries we enrolled adults and skeletally mature adolescents (aged ≥12 years) weighing at least 45 kg with histologically confirmed and radiographically measurable GCTB, Karnofsky performance status 50% or higher (Eastern Cooperative Oncology Group status 0, 1, or 2), and measurable active disease within 1 year of study enrolment. Patients had surgically unsalvageable GCTB (cohort 1), had surgically salvageable GCTB with planned surgery expected to result in severe morbidity (cohort 2), or were enrolled from a previous study of denosumab for GCTB (cohort 3). Patients received 120 mg subcutaneous denosumab once every 4 weeks during the treatment phase, with loading doses (120 mg subcutaneously) administered on study days 8 and 15 to patients in cohorts 1 and 2 (patients in cohort 3 did not receive loading doses). The primary endpoint was safety in terms of the type, frequency, and severity of adverse events; secondary endpoints included time to disease progression from cohort 1 and the proportion of patients without surgery at month 6 for cohort 2. The safety analysis set included all enrolled patients who received at least one dose of denosumab. This study is registered with ClinicalTrials.gov, number NCT00680992, and has been completed. FINDINGS: Between Sept 9, 2008, and Feb 25, 2016, 532 patients were enrolled: 267 in cohort 1, 253 in cohort 2, and 12 in cohort 3. At data cutoff on Feb 24, 2017, median follow-up was 58·1 months (IQR 34·0-74·4) in the overall patient population, and 65·8 months (40·9-82·4) in cohort 1, 53·4 months (28·2-64·1) in cohort 2, and 76·4 months (61·2-76·5) in cohort 3. During the treatment phase, the most common grade 3 or worse adverse events were hypophosphataemia (24 [5%] of 526 patients), osteonecrosis of the jaw (17 [3%], pain in extremity (12 [2%]), and anaemia (11 [2%]). Serious adverse events were reported in 138 (26%) of 526 patients; the most common were osteonecrosis of the jaw (17 [3%]), anaemia (6 [1%]), bone giant cell tumour (6 [1%]), and back pain (5 [1%]). 28 (5%) patients had positively adjudicated osteonecrosis of the jaw, four (1%) had atypical femur fracture, and four (1%) had hypercalcaemia occurring 30 days after denosumab discontinuation. There were four cases (1%) of sarcomatous transformation, consistent with historical data. Ten (2%) treatment-emergent deaths occurred (two of which were considered treatment-related; bone sarcoma in cohort 2 and sarcoma in cohort 1). Median time to progression or recurrence for patients in cohort 1 during the first treatment phase was not reached (28 [11%] of 262 patients had progression or recurrence). 227 (92%; 95% CI 87-95) of 248 patients who received at least one dose of denosumab in cohort 2 had no surgery in the first 6 months of the study. INTERPRETATION: The types and frequencies of adverse events were consistent with the known safety profile of denosumab, which showed long-term disease control for patients with GCTB with unresectable and resectable tumours. Our results suggest that the overall risk to benefit ratio for denosumab treatment in patients with GCTB remains favourable. FUNDING: Amgen.

Assessment of denosumab treatment effects and imaging response in patients with giant cell tumor of bone.

BACKGROUND: Denosumab has been shown to reduce tumor size and progression, reform mineralized bone, and increase intralesional bone density in patients with giant cell tumor of bone (GCTB); however, radiologic assessment of tumors in bone is challenging. The study objective was to assess tumor response to denosumab using three different imaging parameters in a prespecified analysis in patients with GCTB from two phase 2 studies. METHODS: The studies enrolled adults and adolescents (skeletally mature and at least 12 years of age) with radiographically measurable GCTB that were given denosumab 120 mg every 4 weeks, with additional doses on days 8 and 15 of cycle 1. The proportion of patients with an objective tumor response was assessed using either Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST), European Organisation for Research and Treatment of Cancer response criteria (positron emission tomography [PET] scan criteria), or inverse Choi density/size (ICDS) criteria. Target lesions were measured by computed tomography or magnetic resonance imaging (both studies), PET (study 2 only), or plain film radiograph (study 2 only). RESULTS: Most patients (71.6%) had an objective tumor response by at least one response criteria. Per RECIST, 25.1% of patients had a response; per PET scan criteria, 96.2% had a response; per ICDS, 76.1% had a response. 68.5% had an objective tumor response ≥ 24 weeks. Using any criteria, crude incidence of response ranged from 56% (vertebrae/skull) to 91% (lung/soft tissue), and 98.2% had tumor control ≥ 24 weeks. Reduced PET avidity appeared to be an early sign of response to denosumab treatment. CONCLUSION: Modified PET scan criteria and ICDS criteria indicate that most patients show responses and higher benefit rates than modified RECIST, and therefore may be useful for early assessment of response to denosumab. TRIAL REGISTRATION: ClinicalTrials.gov Clinical Trials Registry NCT00396279 (retrospectively registered November 6, 2006) and NCT00680992 (retrospectively registered May 20, 2008).

Results of cement versus bone graft reconstruction after intralesional curettage of bone tumors in the skeletally immature patient.

BACKGROUND: Resection of periphyseal tumors in children presents several unique challenges and complications. Injury to the adjacent physis during resection and adjuvant application has been associated with adverse growth-related outcomes including angular deformities and physeal arrest. The appropriate method of reconstructing bone defects after resection is also controversial. To date there is scant literature on the use of polymethylmethacrylate (PMMA) bone cement as a method of reconstruction in children, and few long-term studies exist on the incidence of growth-related complications after reconstruction. The objective of this study is to evaluate the mechanical, oncological, and developmental outcomes of PMMA use in children. METHODS: The authors retrospectively reviewed the medical records and radiographs of 36 skeletally immature patients who underwent intralesional resections of locally aggressive bone tumors. These patients were divided into 17 patients who received reconstruction with PMMA cement, and 19 patients who were reconstructed with bone graft. Follow-up clinical and radiographic evaluations performed after skeletal maturity were reviewed to assess the structural durability, local tumor recurrence rates, reoperation rates, and the incidence of postoperative complications such as deformity, adjacent joint arthrosis, growth arrest, pain, and functional limitation. RESULTS: The average patient age at the time of surgery was 11.79 years (range, 6 to 15 y). The average length of patient follow-up was 5.3 years (range, 2 to 11.5 y). There were no statistically significant differences observed in the rates of reoperation, local tumor recurrence, growth-related complications, adjacent joint arthrosis, or postoperative pain between the 2 groups. There were no postoperative fractures in the cement group, compared to 3 fractures in the bone graft group, although this was not statistically significant. CONCLUSIONS: PMMA cement as a structural augment after resection may be used in the pediatric population for improving the mechanical stability of bone. Cement use is associated with complication rates of arthrosis, local recurrence, and growth complications comparable to those observed with bone grafting. LEVEL OF EVIDENCE: Level III: Retrospective comparison study.

Safety and efficacy of denosumab for adults and skeletally mature adolescents with giant cell tumour of bone: interim analysis of an open-label, parallel-group, phase 2 study.

BACKGROUND: Giant cell tumour of bone (GCTB) is a very rare, aggressive, and progressive osteolytic tumour for which no standard medicinal treatment or chemotherapy exists. We report interim safety and efficacy results from a phase 2 study of denosumab in patients with GCTB. METHODS: We did an international, open-label, parallel-group, phase 2 trial of patients with histologically confirmed GCTB and radiographically measurable active disease. Eligible patients were adults or skeletally mature adolescents with radiographic evidence of at least one mature long bone who were at least 12 years old and weighed at least 45 kg. We divided patients into three cohorts--those with surgically unsalvageable GCTB (cohort 1), those with salvageable GCTB whose surgery was associated with severe morbidity (cohort 2), and those who transferred from a previous study of denosumab for GCTB (cohort 3). Patients in cohorts 1 and 2 received 120 mg of subcutaneous denosumab every 4 weeks with loading doses on days 8 and 15 of the first cycle; those in cohort 3 continued the regimen from the previous study. Investigator-determined disease status and clinical benefit were assessed every 4 weeks. Our primary endpoint was the safety profile of denosumab in terms of adverse events and laboratory abnormalities. Prespecified secondary endpoints were time to disease progression in cohort 1 and the proportion of patients without any surgery at 6 months in cohort 2. Safety analyses included all patients who received at least one dose of denosumab. Efficacy analyses included all eligible patients who received at least one dose of denosumab. This study is registered with ClinicalTrials.gov, identifier NCT00680992. FINDINGS: 282 patients, including ten adolescents, were included between Sept 9, 2008, and March 25, 2011. Of the 281 patients analysable for safety, three (1%) had osteonecrosis of the jaw and 15 (5%) hypocalcaemia. The most common grade 3-4 adverse events were hypophosphataemia, which occurred in nine (3%) patients, and anaemia, back pain, and pain in extremities, each of which occurred in three patients (1%). Serious adverse events were reported in 25 (9%) patients. No treatment-related deaths were reported. On the basis of investigators' assessment of disease status, 163 of 169 (96%) analysable patients in cohort 1 had no disease progression after median follow-up of 13 months (IQR 5·8-21·0). In cohort 2, 74 of 100 (74%) analysable patients had no surgery and 16 of 26 (62%) patients who had surgery underwent a less morbid procedure than planned. Median follow-up in cohort 2 was 9·2 months (IQR 4·2-12·9). INTERPRETATION: Adverse events were consistent with the known safety profile of denosumab. Denosumab was associated with tumour responses and reduced the need for morbid surgery in patients with GCTB. Denosumab represents a new treatment option for patients with GCTB. FUNDING: Amgen.

Skeletal Muscle Measurements in Pediatric Hematology and Oncology: Essential Components to a Comprehensive Assessment.

Children with hematologic and oncologic health conditions are at risk of impaired skeletal muscle strength, size, and neuromuscular activation that may limit gross motor performance. A comprehensive assessment of neuromuscular function of these children is essential to identify the trajectory of changes in skeletal muscle and to prescribe therapeutic exercise and monitor its impact. Therefore, this review aims to (a) define fundamental properties of skeletal muscle; (b) highlight methods to quantify muscle strength, size, and neuromuscular activation; (c) describe mechanisms that contribute to muscle strength and gross motor performance in children; (d) recommend clinical assessment measures; and (e) illustrate comprehensive muscle assessment in children using examples of sickle cell disease and musculoskeletal sarcoma.

Quantifying muscle strength, size, and neuromuscular activation in adolescent and young adult survivors of musculoskeletal sarcoma: Identifying correlates and responses to functional strengthening.

BACKGROUND: Medical and surgical treatment for musculoskeletal sarcoma (MSS) place survivors at risk for impairments in muscle properties including muscle strength, muscle size, and neuromuscular activation. The purpose of this study was to explore muscle properties, gross motor performance, and quality of life (QoL) and the changes in response to a 6-week functional strengthening intervention (PT-STRONG) in MSS survivors of childhood cancer (CCS). METHODS: Eight lower extremity MSS CCS (13-23 years old) performed baseline testing and three completed PT-STRONG. Participants completed measurements of knee extension strength using handheld dynamometry, vastus lateralis (VL) and rectus femoris (RF) muscle thickness using ultrasonography at rest, and neuromuscular activation using electromyography during strength testing and a step-up task. Participants also completed gross motor and QoL assessments. RESULTS: Compared with the non-surgical limb, MSS CCS had lower surgical limb knee extension strength, VL muscle thickness, and RF step-up muscle rate of activation (RoA). Compared with normative values, MSS CCS had decreased bilateral knee extension strength, gross motor performance, and physical QoL. Positive correlations among muscle strength, muscle thickness, and gross motor performance were identified. After PT-STRONG, MSS CCS had improvements in VL muscle thickness, VL and RF RoA duing step-up, gross motor performance, and physical QoL. CONCLUSIONS: Positive association between larger muscle thickness with greater knee extension strength, and higher knee extension strength with better gross motor performance indicate that comprehensive physical therapy assessment and interventions that identify and target impairments in muscle properties to guide clinical decision making should be considered for MSS CCS into survivorship.

Aseptic loosening rates in distal femoral endoprostheses: does stem size matter?

BACKGROUND: Long-term survival of distal femoral endoprosthetic replacements is largely affected by aseptic loosening. It is unclear whether and to what degree surgical technique and component selection influence the risk of loosening. QUESTIONS/PURPOSES: We (1) established the overall failure and aseptic loosening rates in a tumor population and asked (2) whether stem diameter and specifically the diaphysis-to-stem ratio predicts loosening, and (3) whether resection percentage correlates with failure. METHODS: We retrospectively reviewed the charts of all 93 patients in whom 104 distal femoral replacements had been performed from 1985 to 2008. We extracted the following data: age, need for revision surgeries, tumor diagnosis, adjunct treatment, and implant characteristics. We reviewed radiographs and determined stem size, bone diaphyseal width, and resection percentage of the femur. Kaplan-Meier survivorship was calculated for all implant failures and failures resulting from aseptic loosening. We evaluated radiolucent lines in patients with radiographic followup over 5 years. We identified independent risk factors for loosening. The minimum followup for radiographic evaluation was 5 years (mean, 12.7 years; range, 5.4-23.5 years). RESULTS: Overall implant survival for 104 stems in 93 patients was 73.3% at 10 years, 62.8% at 15 years, and 46.1% at 20 years. Survival from aseptic loosening was 94.6% at 10 and 15 years and 86.5% at 20 years. Of the variables analyzed, only bone:stem ratio independently predicted aseptic failure. Patients with stable implants had larger stem sizes and lower bone:stem ratios than those with loose implants (14.5 mm versus 10.7 mm and 2.02 versus 2.81, respectively). CONCLUSIONS: Our data suggest durability relates to selecting stems that fill the canal. LEVEL OF EVIDENCE: Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Bilateral synchronous tibial periosteal osteosarcoma with familial incidence.

Multifocal or multicentric osteosarcoma (OS) has been described as tumor occurrence at two or more sites in a patient without visceral metastasis. These may be synchronous (more than one lesion at presentation) or metachronous (new tumor developing after the initial treatment). The incidence of multifocal OS has ranged from 1.5 to 5.4% in large series, with the synchronous type being rarer. Similarly, periosteal OS is another rare subtype of surface OS and constitutes less than 2% of all OS. An 11-year-old female was diagnosed with bilateral synchronous tibial periosteal OS, which were confirmed by CT-guided biopsies. After neoadjuvant chemotherapy, the patient underwent a staged wide local resection of the tumors. The defect was reconstructed with a proximal tibial replacement on the left side and autologous bone grafting on the right side. The patient did well after surgery and is free of disease at 5.5 years of follow-up. However, her brother also developed a right tibial periosteal osteosarcoma 4 years after her index surgery. Genetic analysis of blood sample from both patients showed a similar missense mutation in at least one allele of TP53 gene (exon 8). To the best of our knowledge, a case of bilateral 'synchronous' periosteal OS with a familial incidence has not been reported before.

Extensile posterior approach to the ankle with detachment of the achilles tendon for oncologic indications.

BACKGROUND: We describe an extensile posterior approach to the ankle with detachment of the Achilles tendon for resection of extensive tumors involving the posterior ankle. To the best of our knowledge, this approach and its results have not been reported for oncologic indications. METHODS: The surgical technique involved detachment of the Achilles tendon, tumor resection and reconstruction of the Achilles tendon with anchor sutures, and was used in six patients. The diagnosis was pigmented villonodular synovitis (5) and chondroblastoma (1). RESULTS: At a mean of 6 (range, 2 to 10) years followup, all patients were free from tumor. All patients could walk an unlimited amount without any support. There were no problems with Achilles incompetence. The mean Musculoskeletal Tumor Society score was 97 ± 4.2% (range, 90 to 100) and the mean Achilles Tendon Total Rupture Score was 95 ± 5.7 (range, 87 to 100). One patient with screwed suture anchors had backing out of two anchors along with deep infection, requiring surgical debridement and anchor removal. One other patient had a post-traumatic small wound dehiscence which responded to local wound care. CONCLUSION: Excellent exposure, tumor control and patient function were achieved by this approach in a select group of patients. The surgical technique described in this report offers another alternative for an extensile posterior approach to the ankle and/or subtalar joints.

Radiolucent Implants for Fixation of Impending and Pathologic Fractures.

Radiolucent implants offer theoretical advantages of increased ability to evaluate the fracture site for healing and recurrence and potentially less effect on radiation treatment, avoiding scatter. Their clinical utility and outcomes have yet to be proven in a well-designed randomized trial or large cohort study, although studies based on other indications have shown relative safety and they are approved by the US Food and Drug Administration for treatment of pathologic fractures. Further research is necessary to better understand when and how these implants should be implemented in practice. [Orthopedics. 2022;45(3):e115-e121.].

Metaphyseal and diaphyseal chondroblastomas.

OBJECTIVE: Epiphyseal/apophyseal locations are important diagnostic radiological features of chondroblastomas (CB). Although the tumor may secondarily involve the metaphysis, reports of primary metaphyseal or diaphyseal CB without any epiphyseal or apophyseal involvement are exceptionally rare and frequently present as a diagnostic dilemma. The purpose of this study was to present seven cases of pure metaphyseal and/or diaphyseal CB along with a review of pertinent literature. METHODS: A retrospective review of databases at two major referral centers revealed 390 cases of CB between 1960 and 2009. Out of these, seven histologically proven CB cases (1.8%) were found to be radiologically located in metaphysis and/or diaphysis, without involving the epiphysis and/or apophysis, and formed the study cohort. RESULTS: There were four males and three females (age range 2-25 years). Locations included proximal femur (n = 1), distal femur (2), proximal humerus (2), clavicle (1), and proximal radius (1). All lesions showed marginal sclerosis. A periosteal reaction was seen in five cases (71%), cortical expansion in four cases (57%), and chondroid matrix in four cases (57%). A CT (two cases) demonstrated a matrix in both cases. An MR (one case) showed extensive perilesional edema. Bone scan (one case) showed intense uptake. CONCLUSION: Pure metaphyseal and/or diaphyseal CB are exceedingly rare. A presumptive diagnosis may be considered in the appropriate age group in the presence of chondroid matrix, perilesional edema, periosteal reaction, and marginal sclerosis. Regardless of all the diagnostic possibilities, biopsy may still be required. However, knowledge of this entity will help make the final diagnosis and guide the correct treatment.

Denosumab in patients with giant-cell tumour of bone: an open-label, phase 2 study.

BACKGROUND: Giant-cell tumour (GCT) of bone is a primary osteolytic bone tumour with low metastatic potential and is associated with substantial skeletal morbidity. GCT is rich in osteoclast-like giant cells and contains mononuclear (stromal) cells that express RANK ligand (RANKL), a key mediator of osteoclast activation. We investigated the potential therapeutic effect of denosumab, a fully human monoclonal antibody against RANKL, on tumour-cell survival and growth in patients with GCT. METHODS: In this open-label, single-group study, 37 patients with recurrent or unresectable GCT were enrolled and received subcutaneous denosumab 120 mg monthly (every 28 days), with loading doses on days 8 and 15 of month 1. The primary endpoint was tumour response, defined as elimination of at least 90% of giant cells or no radiological progression of the target lesion up to week 25. Study recruitment is closed; patient treatment and follow-up are ongoing. The study is registered with Clinical Trials.gov, NCT00396279. FINDINGS: Two patients had insufficient histology or radiology data for efficacy assessment. 30 of 35 (86%; 95% CI 70-95) of evaluable patients had a tumour response: 20 of 20 assessed by histology and 10 of 15 assessed by radiology. Adverse events were reported in 33 of 37 patients; the most common being pain in an extremity (n=7), back pain (n=4), and headache (n=4). Five patients had grade 3-5 adverse events, only one of which (grade 3 increase in human chorionic gonadotropin concentration not related to pregnancy) was deemed to be possibly treatment related. Five serious adverse events were reported although none were deemed treatment related. INTERPRETATION: Further investigation of denosumab as a therapy for GCT is warranted. FUNDING: Amgen, Inc.

Early Experience in Pathologic Humerus Fracture Treated With the Photodynamic Bone Stabilization System Shows Limitations Related to Patient Selection.

Impending and complete pathologic fractures often necessitate surgical fixation. Traditional orthopedic implants are commonly used, achieving clinically acceptable outcomes, but their metallic composition can impair radiographic evaluation and affect radiation treatments. Recognition of these concerns led to the development of radiolucent implants such as the minimally invasive Photodynamic Bone Stabilization System (PBSS; IlluminOss Medical Inc), featuring a light cured polymer contained within an inflatable balloon catheter. Two participating hospitals in one health care system reviewed cases using the PBSS implant. Twenty-five patients with 29 impending or pathologic fractures in the proximal radius or humerus from metastatic carcinoma, myeloma, lymphoma, and melanoma were identified. Clinical charts and imaging were reviewed to determine the status of the implant at final follow-up as well as complications. For analysis, a chi-square test was used for nominal variables and a t test was used for continuous variables. Eleven of the 25 patients were alive with disease at the time of analysis. Eight of 29 (27.5%) implants failed. Five of 25 (20%) patients required repeat surgery due to complications, including 3 revision open reduction and internal fixations, 1 open reduction and internal fixation for a periprosthetic fracture, and 1 screw removal. Five of the 9 cases (56%) (P=.03) with lesions in the distal humeral shaft had breakage of the implant by final follow-up, compared with 3 of 20 cases (15%) (P=.03) elsewhere in the humerus; no failures were seen in the radius. One of 4 patients (25%) also had failure in the surgical neck, although this did not reach significance. Five patients were noted to have progression of disease on follow-up radiographs, with 4 failures in patients with progression. The PBSS implants potentially allow improved surveillance of fracture healing and tumor recurrence along with decreased scattering of radiation during treatment. Unfortunately, there may be a higher rate of mechanical failures, particularly for lesions involving the distal humerus. This may be due to decreased cross-sectional area of the implant in this region as compared with the metaphyseal and proximal regions. Caution should be exercised when treating distal humeral pathologic fractures with large lytic lesions where the underlying disease process is not well controlled. [Orthopedics. 2021;44(3):154-159.].

Denosumab Treatment for Giant Cell Tumor of the Spine Including the Sacrum.

STUDY DESIGN: This was a subanalysis of an international, multicenter, open-label study. OBJECTIVE: The aim of this study was to assess the efficacy and safety of denosumab in a subset of patients with giant cell tumors of bone (GCTB) of the spine including the sacrum from an international, open-label, single-arm, phase 2 study (ClinicalTrials.gov: NCT00680992). SUMMARY OF BACKGROUND DATA: Standard GCTB treatment is surgical removal, either by curettage or resection, combined with intraoperative adjuvant therapy; however, some sites may not be amenable to resection (e.g., skull, spine). METHODS: Adults or skeletally mature adolescents with pathologically confirmed GCTB of the spine including the sacrum, and radiologically measurable evidence of active disease, were included. Patients received denosumab (120 mg subcutaneously) once every 4 weeks during the treatment phase, with loading doses on days 8 and 15 of the first cycle. Patients had surgically unsalvageable GCTB (Cohort 1), had planned surgery expected to result in severe morbidity (Cohort 2), or were enrolled from a previous GCTB study (Cohort 3). RESULTS: Overall, 132 patients were included in the safety analysis (103 in Cohort 1, 24 in Cohort 2, and five in Cohort 3); 131 patients were included in the efficacy analysis. Kaplan-Meier estimated probabilities of disease progression or recurrence were 3% (95% confidence interval [CI], 0.0-6.2) at year 1 and 7.4% (95% CI, 2.1-12.7) at years 3 and 5 in Cohort 1, and not estimable in Cohorts 2 and 3. Of 23 patients (Cohort 2) with surgery planned at baseline, 10 (43%) had on-study surgery; of these, one patient had reported disease progression or recurrence after the on-study surgery. Clinical benefit was reported in 83% of patients overall (all cohorts). CONCLUSION: Results from the analysis suggest that denosumab is potentially effective treatment for patients with GCTB of the spine including the sacrum. The adverse event profile was consistent with the full study population.Level of Evidence: 2.

Late complications and survival of endoprosthetic reconstruction after resection of bone tumors.

BACKGROUND: While complications following massive endoprosthetic reconstruction have been previously described, the incidence and effects of these complications over extended periods of time have not been well characterized in large series. QUESTIONS/PURPOSES: We therefore determined: (1) incidence and types of complications; (2) relative risk of complications; (3) likelihood of secondary complications; (4) whether modularity altered such complications; (5) implant failure and limb salvage rates and (6) implant survival over extended followup. METHODS: We retrospectively reviewed 232 patients (241 implants: 50 custom,191 modular) who underwent endoprosthetic reconstruction for malignant and aggressive bone tumors between 1980 and 2002. Complications were classified as infection, mechanical, superficial soft tissue, deep soft tissue, or dislocation. Survival was determined by Kaplan-Meier analysis. Minimum followup was 5 years (mean: 10 years; range: 5-27 years). RESULTS: One hundred thirty-seven of 232 patients (59%) underwent a single reconstruction. Ninety-five patients had 242 additional procedures. Forty-four revised patients retained their original prosthesis. Limb salvage rate was 90%; implant failure (removal of the cemented part) was seen in 29% (70/241) with a median survival of 190 months. Twenty-five of 50 custom implants failed (8 then failed again) while 30/180 modular implants failed (7 then failed again). Of 70 instances of implant failure, 38/70 were mechanical, 27/70 infectious. Risk of infection increased 30% after a second procedure; 16 of 24 amputations were performed because of infection. CONCLUSIONS: Mechanical complications were the most common cause of implant failure. Infection was the leading cause of both complication and amputation; risk of infection increased substantially with revision surgery. Modular implants had fewer mechanical complications, thus leading to fewer revisions and subsequent infections.

Metastatic prostate carcinoma: A rare presentation initially misdiagnosed as a rib fracture.

Metastatic prostate carcinoma mainly occurs in bone as an osteoblastic lesion or lesions in the pelvis, spine, or chest wall. We present a unique case of a singular metastatic osteolytic lesion in the rib initially misdiagnosed as a fracture in a 61-year-old male. A single rib fracture in a patient with no history of trauma should raise suspicion for metastatic disease. We would encourage prostate cancer to be included in the differential diagnosis for an osteolytic lesion in a male over the age of 40. We review the current literature on this rare presentation of bone metastasis as well as the pathogenesis of metastatic prostate carcinoma as it relates to a solitary metastatic osteolytic lesion.

Alterations in Muscle Architecture: A Review of the Relevance to Individuals After Limb Salvage Surgery for Bone Sarcoma.

Osteosarcoma and Ewing's sarcoma are the most common primary bone malignancies affecting children and adolescents. Optimal treatment requires a combination of chemotherapy and/or radiation along with surgical removal when feasible. Advances in multiple aspects of surgical management have allowed limb salvage surgery (LSS) to supplant amputation as the most common procedure for these tumors. However, individuals may experience significant impairment after LSS, including deficits in range of motion and strength that limit function and impact participation in work, school, and the community, ultimately affecting quality of life. Muscle force and speed of contraction are important contributors to normal function during activities such as gait, stairs, and other functional tasks. Muscle architecture is the primary contributor to muscle function and adapts to various stimuli, including periods of immobilization-protected weightbearing after surgery. The impacts of LSS on muscle architecture and how adaptations may impact deficits within the rehabilitation period and into long-term survivorship is not well-studied. The purpose of this paper is to [1] provide relevant background on bone sarcomas and LSS, [2] highlight the importance of muscle architecture, its measurement, and alterations as seen in other relevant populations and [3] discuss the clinical relevance of muscle architectural changes and the impact on muscle dysfunction in this population. Understanding the changes that occur in muscle architecture and its impact on long-term impairments in bone sarcoma survivors is important in developing new rehabilitation treatments that optimize functional outcomes.

Hypocalcemia in a patient with osteosarcoma and 22q11.2 deletion syndrome.

Hypocalcemia is a rare complication of osteosarcoma, having been described in only 4 reports. We present the case of a 16-year-old male with metastatic osteosarcoma of the right humerus who was found to have severe asymptomatic hypocalcemia. Cytogenetic analysis of peripheral blood revealed a microdeletion in band 22q11.2. Following amputation of the tumor-bearing extremity, the patient's calcium levels increased, but did not normalize. These findings suggested that the etiology of his hypocalcemia was osteoblastic utilization of calcium by the tumor, exacerbated by 22q11.2 deletion syndrome.

Implant design and resection length affect cemented endoprosthesis survival in proximal tibial reconstruction.

Endoprosthetic reconstruction of the proximal tibia continues to pose many challenges. A retrospective analysis of 44 consecutive patients who underwent cemented proximal tibial replacement were included to investigate if patient age, surgical stage, type of implant, stem diameter, or resection length could be associated with implant failure. Fifteen patients (34%) suffered prosthetic failure, 7 due to infection. Prosthetic-related complications occurred in 13 patients (30%). Custom design prosthesis and longer length of resection were significantly associated with prosthesis survival in a Cox regression analysis (P = .001, hazard ratio = 8.747 and P = .044, hazard ratio = 1.217, respectively). Cemented proximal tibial replacement offers a functional knee, but reducing risk of complications still remains challenging. Prosthetic design and length of resection affect overall cemented endoprosthesis survival.