Larger stem to bone diameter ratio predicts lower cemented endoprosthesis failure.

BACKGROUND AND OBJECTIVES: With continued advances in treatment options, patients with endoprosthetic reconstruction are living longer and consequently relying upon their devices for a longer duration. Major causes of endoprosthesis failure include aseptic loosening and mechanical failure. In the setting of tumor resection, loss of bone stock and use of radiation therapy increase the risk for these complications. As such, considerations of remaining native bone and stem length and diameter may be increasingly important. We asked the following questions: (1) What was the overall rate of endoprosthesis failure at a minimum of 5-year follow-up? (2) Does resection length increase implant failure rates? (3) Does implant size and its ratio to cortical width of bone alter implant failure rates? METHODS: We retrospectively analyzed patient outcomes at a single institution between the years of 1999-2022 who underwent cemented endoprosthetic reconstruction at the hip or knee and identified 150 patients. Of these 150, 55 had a follow-up of greater than 5 years and were used for analysis. Radiographs of these patients at time of surgery were assessed and measured for resection length, bone diameter, stem diameter, and remaining bone length. Resection percentage, and stem to bone diameter ratios were then calculated and their relationship to endoprosthesis failure were analyzed. RESULTS: Patients in this cohort had a mean age of 55.8, and mean follow-up of 59.96 months. There were 78 distal femoral replacements (52%), 16 proximal femoral replacements (10.7%), and 56 proximal tibial replacements (37.3%). There were five patients who experienced aseptic loosening and six patients who experienced mechanical failure. Patients with implant failure had a smaller mean stem to bone diameter (36% vs. 44%; p = 0.002). A stem to bone diameter of 40% appeared to be a breaking point between success and failure in this series, with 90% of patients with implant failure having a stem: bone ratio less than 40%. Stem to bone ratio less than 40% increased risk for failure versus stems that were at least 40% the diameter of bone (6/19 [31.6%] vs. 0/36 [0%]; odds ratio 0.68; p < 0.001). Resection length did not appear to have an impact on the rates of aseptic loosening and mechanical failure in this series. CONCLUSIONS: Data from this series suggests a benefit to using stems with a larger diameter when implanting cemented endoprostheses at the hip or knee. Stems which were less than 40% the diameter of bone were substantially more likely to undergo implant failure.

IVC filter placement in patients undergoing surgical treatment of bone or soft-tissue tumors.

BACKGROUND AND OBJECTIVES: Patients with cancer to bone or soft tissues undergoing orthopedic procedures may be unable to receive pharmacologic prophylaxis for venous thromboembolism (VTE). Inferior vena cava (IVC) filters may be an effective method to prevent fatal pulmonary embolism (PE) in these patients. METHODS: Retrospective chart review performed for patients surgically treated for malignant disease of bone or soft tissue who had IVC filter placement. Type of surgery, anatomic region, and development of wound complications requiring repeat surgery were analyzed. RESULTS: From 2007 to 2018, 286 patients received IVC filters. Ten (3.5%) patients suffered deep vein thrombus (DVT) postoperatively. There was no acute fatal PE. Two patients suffered PE at 2 and 99 days postoperatively. Risk of DVT was comparable following surgery with endoprosthesis versus open reduction and internal fixation (p = 0.056) and with soft tissue versus bone involvement (p = 0.620). Three filter-related complications occurred. Patients disease at the femur had the highest rate of DVT. CONCLUSIONS: Following treatment of malignant disease of bone or soft-tissues, two patients with IVC filter placement experienced nonfatal PE and three patients experienced filter-related complications. No patients in this series experienced a fatal PE.

Management of Large Segmental Bone Defects at the Knee With Intramedullary Stabilized Antibiotic Spacers During Two-Stage Treatment of Endoprosthetic Joint Infection.

BACKGROUND: Following debridement of infected prostheses that require reconstruction with an endoprosthetic replacement (EPR), instability related to segmental residual bone defects present a challenge in management with 2-stage reimplantation. METHODS: We retrospectively reviewed all patients treated for revision total joint or endoprosthetic infection at the knee from 1998 to 2018. At our institution, patients with skeletal defects >6 cm following explant of prosthesis and debridement (stage 1) were managed with intramedullary nail-stabilized antibiotic spacers. Following stage 1, antimicrobial therapy included 6 weeks of intravenous antibiotics and a minimum of 6 weeks of oral antibiotics. Following resolution of inflammatory markers and negative tissue cultures, reimplantation (stage 2) of an EPR was performed. RESULTS: Twenty-one patients at a mean age of 54 ± 21 years were treated for prosthetic joint infection at the knee. Polymicrobial growth was detected in 38% of cases, followed by coagulase-negative staphylococci (24%) and Staphylococcus aureus (19%). Mean residual skeletal defect after stage 1 treatment was 20 cm. Prosthetic joint infection eradication was achieved in 18 (86%) patients, with a mean Musculoskeletal Tumor Society score of 77% and mean knee range of motion of 100°. Patients with polymicrobial infections had a greater number of surgeries prior to infection (P = .024), and were more likely to require additional debridement prior to EPR (odds ratio 12.0, P = .048). CONCLUSION: Management of large segmental skeletal defects at the knee following explant using intramedullary stabilized antibiotic spacers maintain stability and result in high rates of limb salvage with conversion to an endoprosthesis.

Outcomes following periacetabular tumor resection: A 25-year institutional experience.

BACKGROUNDS AND OBJECTIVES: Following tumor resection involving the acetabulum (periacetabular), various methods of reconstruction exist. The objective of this study was to analyze functional outcomes and complication rates by extent of periacetabular tumor resection, as well as by method of reconstruction. METHODS: Twenty-three patients underwent periacetabular resection for a primary pelvic bone tumor from 1993-2018 at a single institution. Complications were documented and functional outcomes were assessed using the Musculoskeletal Tumor Society (MSTS) scoring system. RESULTS: Mean age was 42.8 ± 22.6 years. Mean follow-up was 107 ± 75 months. MSTS scores were highest in patients with allograft reconstruction (80.2%) and lowest in saddle reconstruction (38.0%). MSTS scores were higher in patients with Type II periacetabular resection alone compared with Type II + additional resection (78.6% vs 60.3%; P = .019). Complications were lower in patients with Type II periacetabular resection alone (75% vs 28.6%; P = .036). Complications were highest following allograft reconstruction (78%) and lowest following hemipelvectomy without reconstruction (20%). CONCLUSION: Patients who underwent allograft/APC or nonsaddle metallic reconstruction experienced the highest functional outcome scores, but also sustained a higher complication rate than patients with hemipelvectomy without reconstruction. Patients with resection of ilium and/or pubis in addition to the periacetabular region had lower functional outcome scores and higher risk for complication.

Supplemental Bone Grafting in Giant Cell Tumor of the Extremity Reduces Nononcologic Complications.

BACKGROUND: Giant cell tumors (GCTs) are treated with resection curettage and adjuvants followed by stabilization. Complications include recurrence, fracture, and joint degeneration. Studies have shown treatment with polymethylmethacrylate (PMMA) may increase the risk of joint degeneration and fracture. Other studies have suggested that subchondral bone grafting may reduce these risks. QUESTIONS/PURPOSES: Following standard intralesional resection-curettage and adjuvant treatment, is the use of bone graft, with or without supplemental PMMA, (1) associated with fewer nononcologic complications; (2) associated with differences in tumor recurrence between patients treated with versus those treated without bone grafting for GCT; and (3) associated with differences in Musculoskeletal Tumor Society (MSTS) scores? METHODS: Between 1996 and 2014, 49 patients presented with GCT in the epiphysis of a long bone. Six patients were excluded, four who were lost to followup before 12 months and two because they presented with displaced, comminuted, intraarticular pathologic fractures with a nonreconstructable joint surface. The remaining 43 patients were included in our study at a mean followup of 59 months (range, 12-234 months). After resection-curettage, 21 patients were reconstructed using femoral head allograft with or without PMMA (JB) and 22 patients were reconstructed using PMMA alone (FRP, KSB); each surgeon used the same approach (that is, bone graft or no bone graft) throughout the period of study. The primary study comparison was between patients treated with bone graft (with or without PMMA) and those treated without bone graft. RESULTS: Nononcologic complications occurred less frequently in patients treated with bone graft than those treated without (10% [two of 21] versus 55% [12 of 22]; odds ratio, 0.088; 95% confidence interval [CI], 0.02-0.47; p = 0.002). Patients with bone graft had increased nononcologic complication-free survival (hazard ratio, 4.59; 95% CI, 1.39-15.12; p = 0.012). With the numbers available, there was no difference in tumor recurrence between patients treated with bone graft versus without (29% [six of 21] versus 32% [seven of 22]; odds ratio, 0.70; 95% CI, 0.1936-2.531; p = 0.586) or in recurrence-free survival among patients with bone graft versus without (hazard ratio, 0.94; 95% CI, 0.30-2.98; p = 0.920). With the numbers available, there was no difference in mean MSTS scores between patients treated with bone graft versus without (92% ± 2% versus 93% ± 1.4%; mean difference 1.0%; 95% CI, -3.9% to 6.0%; p = 0.675). CONCLUSIONS: Compared with PMMA alone, the use of periarticular bone graft constructs reduces postoperative complications apparently without increasing the likelihood of tumor recurrence. LEVEL OF EVIDENCE: Level III, therapeutic study.

Outcomes of a Modular Intercalary Endoprosthesis as Treatment for Segmental Defects of the Femur, Tibia, and Humerus.

BACKGROUND: Resection of diaphyseal bone tumors for local tumor control and stabilization often results in an intercalary skeletal defect and presents a reconstructive challenge for orthopaedic surgeons. Although many options for reconstruction have been described, relatively few studies report on the functional outcomes and complications of patients treated with modular intercalary endoprostheses. QUESTIONS/PURPOSES: The objectives of this study were to examine clinical outcomes after reconstruction with a modular intercalary endoprosthesis with a specific focus on (1) the rate of complication or failure; (2) differences in complication rates by anatomic site; (3) functional results as assessed by the Musculoskeletal Tumor Society System (MSTS); and (4) differences in complication rate between patients treated with cemented versus noncemented fixation. METHODS: We conducted a retrospective chart review of patients treated with a modular intercalary endoprosthesis from three musculoskeletal oncology centers from 2008 to 2013. The indication for use of this intercalary endoprosthesis was segmental bone loss from aggressive or malignant tumor with sparing of the joint above and below and deemed unsuitable for biologic reconstruction. No other implant was used for this indication during this period. During this period, 41 patients received a total of 44 intercalary implants, which included 18 (40%) humeri, 5 (11%) tibiae, and 21 (48%) femora. There were 27 (66%) men and 14 (34%) women with a mean age of 63 years (range, 18­91 years). Eight patients (20%) had primary bone tumors and 33 (80%) had metastatic lesions. Thirty-five (85%) patients were being operated on as an initial treatment and six (15%) for revision of a previous reconstruction. Twenty-nine (66%) procedures had cemented stem fixation and 15 (34%) were treated with noncemented fixation. The overall mean followup was 14 months (range, 1­51 months). Patients with primary tumors had a mean followup of 19 months (range, 4­48 months) and patients with metastatic disease had a mean followup of 11 months (range, 1­51 months). Causes of implant failure were categorized according to Henderson et al. [19] into five types as follows: Type I (soft tissue failure), Type II (aseptic loosening), Type III (structural failure), Type IV (infection), and Type V (tumor progression). At 2 years of followup, 38 (93%) of these patients were accounted for with three (7%) lost to followup. MSTS functional assessment was available for 39 of 41 patients (95%). RESULTS: At latest followup of these 41 patients, 14 (34%) patients were dead of disease, two patients (5%) dead of other causes, seven (17%) are continuously disease-free, one (2%) shows no evidence of disease, and 17 (41%) are alive with disease. There were 12 (27%) nononcologic complications. Five (11%) of these were Type II failures occurring in noncemented implants between the stem and bone, and six (14%) were Type III failures occurring in cemented implants at the clamp-rod implant interface. One patient developed a deep infection (2%, Type IV failure) and underwent removal of the implant. Additionally, one patient (2%, Type V failure) was treated by amputation after local progression of his metastatic disease. Complications were more common in femoral reconstructions than in tibial or humeral reconstructions. Twelve of 21 patients (57%) with femoral reconstructions had complications versus 0% of tibial or humeral reconstructions (0 of 23; odds ratio [OR], 62; 95% confidence interval [CI], 3­1154; p < 0.0001). The mean overall MSTS score was 77%. Implants with cemented fixation (29) had higher mean MSTS scores when compared with implants with noncemented (15) fixation (84% versus 66%, p = 0.0017). The complication rate was 33% in noncemented cases and 21% in cemented cases (p = 0.39); however, Type II failure at the bone-stem interface was associated with noncemented fixation and Type III failure at the clamp-rod interface was associated with cemented fixation (OR, 143; 95% CI, 2.413­8476; p = 0.0022). CONCLUSIONS: The results of this study indicate that this modular intercalary endoprosthesis yields equivalent results to other studies of intercalary endoprostheses in terms of MSTS scores. We found that patients treated with intercalary endoprostheses in the femur experienced more frequent complications than those treated for lesions in either the humerus or tibia and that the femoral complication rate of this endoprosthesis is higher when compared with other studies of intercalary endoprostheses for femoral reconstruction. Further studies are still needed to determine the long-term outcomes of this endoprosthesis in patients with primary tumors where longevity of the implant is of more importance than in the metastatic setting. We recommend cemented fixation for this intercalary modular endoprostheses because this provides improved MSTS scores and allows immediate return to weightbearing, which is of advantage to metastatic patients with limited lifespans. Level of Evidence: Level III, therapeutic study.

Steinmann pin augmentation versus locking plate constructs.

BACKGROUND: Aggressive bone neoplasms, such as giant cell tumors, often affect the proximal tibia warranting bony resection via curettage leaving behind massive defects that require extensive reconstruction. Reconstruction is usually accomplished with poly(methyl methacrylate) (PMMA) packing supplemented with an internal fixation construct. The purpose of this study is to compare Steinmann pin augmentation to locking plate constructs to determine which offers the stiffer reconstruction option. MATERIALS AND METHODS: Large defects were created below the lateral condyle of fresh frozen tibias. The defects extended for an average of 35 mm beneath the lateral plateau in the frontal plane, and from the anterior to posterior cortex in the sagittal plane. Distally the defect extended for an average of 35 mm to the metadiaphyseal junction. In the Pin group, the tibias were reconstructed with three 4-mm diameter Steinmann pins placed in the medullary canal and PMMA packing. In the Plate group, the tibias were reconstructed with a 6-hole 3.5-mm LCP Proximal locking plate fixed to the proximal-lateral tibia utilizing seven 3.5-mm screws and PMMA packing. The tibias were tested for stiffness on a MTS machine by applying up to 400 N to the tibial plateau in force control at 5 N/s. Fatigue properties were tested by applying a haversine loading waveform between 200 N and 1,200 N at 3 Hz simulating walking upstairs/downstairs. RESULTS: Locking plate constructs (801.8 ± 78 N/mm) had greater (p = 0.041) stiffness than tibial constructs fixed with Steinmann pins (646.5 ± 206.3 N/mm). CONCLUSIONS: Permanent deformation was similar between the Pin and Plate group; however, two tibia from the Pin group exhibited displacements >5 mm which we considered failure. LEVEL OF EVIDENCE: n/a.

Statin-related muscle complications masquerading as soft tissue sarcomas.

Musculoskeletal injuries are a known side effect of long-term statin use. These injuries include sudden, atraumatic muscle rupture which can cause extremity hematomas that motivate patients to seek evaluation and physicians to send referrals for oncologic workup. We discuss two cases where malignancy was suspected rather than statin-induced muscle injury. Using these cases as examples, we discuss subtleties between the two diagnoses so that muscle rupture may be considered prior to subspecialist referral. This paper aims to serve as a reminder and guide for physicians who encounter long-term statin users with nonspecific, improving musculoskeletal symptoms and hemorrhagic MRI findings that lack nodular or mass-like enhancements. While referral to orthopedic oncology is always encouraged in cases of uncertainty, it may not always be necessary.

Cemented-augmented fixation of metastatic humeral lesions without segmental bone loss results in reliable outcomes.

Background: Treatment of metastatic lesions to the humerus is dependent on patient's pain, lesion size and location, and post-operative functional goals. Surgical options include plate or nail fixation [open reduction internal fixation (ORIF)], or endoprosthetic replacement (EPR), with cement augmentation. The objective of this study was to perform a single institution retrospective analysis of outcomes by method of reconstruction, tumor volume, and pathologic diagnosis. Methods: The records of 229 consecutive patients treated surgically for appendicular metastatic disease from 2005-2018 at our musculoskeletal oncology center were retrospectively reviewed following institutional review board (IRB) approval. Indications for surgical treatment at the humerus included patients who presented with impending and displaced pathologic fractures. Results: Sixty patients (34 male, 26 female) with a mean age of 62.9±12.2 were identified who were treated surgically at the proximal (n=21), diaphyseal (n=29), or distal (n=10) humerus. Forty-nine (82%) patients presented with displaced pathologic fractures. The remaining eleven patients had a mean Mirels score of 9.5. There was no difference in overall complication rate between EPR or ORIF [4/36 (11%) versus 2/24 (8%); P=0.725]. Mean Musculoskeletal Tumor Society (MSTS) scores were 83% for both EPR and ORIF, with no differences in subgroup analyses at the proximal, diaphyseal, or distal humerus. Patients with cortical destruction on anterior posterior (AP) and lateral imaging were at increased risk for mechanical failure [2/6 (33%) versus 0/18 (0%), P=0.015]. Conclusions: In conclusion, when pathologic pattern permits, cement-augmented fixation allows for stabilization of pathologic bone, while minimizing risk of soft-tissue detachment, while EPR resulted in similar outcomes in patients with more extensive bone destruction. Increased tumor volume was associated with lower MSTS scores.

Rapid and Complete Response to Combination Anti-CTLA-4 and Anti-PD-1 Checkpoint Inhibitor Therapy in a Patient With Stage IV Refractory End-stage Epithelioid Sarcoma: A Case Report.

Epithelioid sarcoma, in the relapse-refractory setting, has limited expected survival. SMARCB1 inactivation, common in epithelioid sarcoma, causes loss of INI1 protein expression and overexpression of the cancer cell growth promoting methyltransferase enzyme, EZH2. We treated a 19-year-old male with stage IV SMARCB1 inactivated epithelioid sarcoma presenting with recurrent end stage (Eastern Cooperative Oncology Group Performance Status 4) rapidly progressing bulky disease with combination ipilimumab and nivolumab. He failed standard therapy and an EZH2 inhibitor (tazemetostat). He presented (May 13, 2019) with a large (16.1×18.6 cm) soft tissue back mass extending from T10 to L3. Complete clinical regression of the back mass occurred within 2 weeks (May 28, 2019) of cycle 1 of combined checkpoint inhibition therapy followed by a positron emission tomography-negative complete remission (October 11, 2019). After a second negative positron emission tomography/computed tomography scan (January 13, 2020), checkpoint inhibition therapy was discontinued. He has returned to normal activities with a normal physical examination and Eastern Cooperative Oncology Group Performance Status of 0 at his last visit (June 29, 2020). In conclusion, combined checkpoint inhibition therapy warrants further study in the salvage setting in patients with epithelioid and other INI1 protein-deficient sarcomas seemingly regardless of prior therapy, extent of disease, and performance status.

Functional outcomes after limb-salvage surgery and endoprosthetic reconstruction with an expandable prosthesis: a report of 4 cases.

OBJECTIVE: To determine the functional outcomes of skeletally immature patients after replacement of the femur and tibia performed by using noninvasive expandable endoprostheses. DESIGN: Case series. SETTING: A hospital-based ambulatory care center. PARTICIPANTS: Pediatric patients (N=4) with primary bone tumors of the distal femur and proximal tibia who underwent surgical replacement performed by using the Repiphysis noninvasive expandable endoprosthesis (Wright Medical Technology, Memphis, TN). INTERVENTIONS: Wide resection of bone sarcoma and placement of expandable endoprosthesis. MAIN OUTCOME MEASURES: Musculoskeletal Tumor Society (MSTS) scores were assessed at the beginning of the study and at each follow-up visit. Medical Outcomes Study 36-Item Short-Form Health Survey, Version 2 (SF-36); gait; sit-to-stand transition; and range of motion (ROM) were assessed at an average follow-up of 31.5 months. RESULTS: At an average of 31.5 months postoperative, the SF-36 physical component summary scores lagged behind the national mean, whereas the mental component summary scores were satisfactory. MSTS scores indicated low levels of pain and supports use with high emotional acceptance and walking ability but persisting difficulties with function and gait. Patients also showed altered patterns of sit-to-stand transition including decreased peak vertical force in the operated limb and increased center of mass momentum in a shorter amount of time. Parts of gait functioning were found to be decreased, including gait velocity, stride length, and cadence. Some patients displayed alternate weight-bearing strategies that accompanied increased double-limb support and stance phase during walking. ROM and strength were diminished at both the hip and knee joints in the operated limb and in the nonoperated limb. CONCLUSIONS: Reconstruction with a noninvasive expandable endoprosthesis produces satisfactory functional outcomes in pediatric patients with primary tumors of the bone. Patients in our study displayed some persisting physical difficulties including decreased ROM and strength and altered gait and sit-to-stand patterns, yet they maintained high levels of emotional acceptance and coping.

IVC filters may prevent fatal pulmonary embolism in musculoskeletal tumor surgery.

UNLABELLED: To determine whether inferior vena cava (IVC) filter placement protects patients with musculoskeletal tumors from fatal pulmonary embolisms (PE), we retrospectively analyzed the records of 81 patients who underwent surgery for pelvic and lower extremity malignancies. All 81 patients received an IVC filter and mechanical compression for deep venous thrombosis (DVT) prophylaxis, but no pharmacologic anticoagulation. Duplex imaging was performed before hospital discharge and when clinical suspicion of DVT arose. Seventy-six of the 81 (94%) patients were followed at least 3 months (mean, 21.3 months; range, 3-77 months) postoperatively. We reviewed the perioperative medical records and office visit notes to determine the rate of clinically evident DVT, symptomatic PE, wound complications, and IVC filter-related complications. DVT and PE incidences in the early postoperative period (< 30 days) were 21% (17 of 81) and 2% (two of 81), respectively. There were no known deaths from PE. Patients undergoing reconstruction surgery (n = 41) were more likely to have early DVT develop after definitive tumor surgery. Patient age, tumor type or histology, anatomic location, presence of pathologic fracture, or development of wound complications did not correlate with an increased DVT rate. Two (3%) patients had late DVT, and none had a late PE. Combining an IVC filter with mechanical limb compression prevented fatal PE in patients undergoing orthopaedic surgery for malignancies of the pelvis and lower extremity and is a reasonable form of thromboembolic prophylaxis specific for this patient population. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

Complications following allograft reconstruction for primary bone tumors: Considerations for management.

INTRODUCTION: The aim of this study was to investigate complication rates and types following allograft reconstruction and discuss unique considerations for management. METHODS: Seventy-four consecutive patients underwent large segment allograft reconstruction following resection of primary musculoskeletal tumors from 1991 to 2016. Mean patient age was 32 ±â€¯20 years (range, 5-71 years). Minimum follow-up was 2 years unless patients were lost to disease prior. Mean follow-up was 105 months. RESULTS: Thirty-five patients had complications requiring subsequent surgery at a mean of 30 months (range, 1-146 months) post-operatively. Individual complication rates were 29%, 50%, and 42% for Allograft Prosthetic Composite, Intercalary, and Osteoarticular allograft reconstruction, respectively. Risk factors for complication included age less than 30 (OR 4.5; p = 0.002), male gender (OR 2.8; p = 0.031), chemotherapy (OR 4.4; p = 0.003), lower extremity disease (OR 3.4; p = 0.025). In patients with complications, limb-retention rate was 91% and mean MSTS scores were 23.6. CONCLUSION: Despite considerable complication rates, management with a systematic approach results in successful outcomes with limb-retention greater than 90% and mean MSTS scores of 79%. In carefully selected patients, allografts provide a reliable method of reconstruction with treatable complications occurring at a mean of 30 months.

Overall survival advantage of chemotherapy and radiotherapy in the perioperative management of large extremity and trunk soft tissue sarcoma; a large database analysis.

PURPOSE: Intergroup 9514 reported promising outcomes with neoadjuvant chemoradiotherapy for large extremity/trunk soft tissue sarcoma (ESTS). One decade later, optimum integration of chemotherapy and radiotherapy into the perioperative management of ESTS remains to be defined. METHODS: The National Cancer Data Base was used to identify 3422 patients who underwent resection for large (>8cm) high-grade STS between 2004 and 2013. Chi-square analysis was used to evaluate distribution of patient and tumor related factors within treatment groups while multivariate analyses were used to determine the impact of these factors on patient outcome. The Kaplan Meier method and Cox proportional hazards model were utilized to evaluate overall survival according to treatment regimen, with a secondary analysis based on propensity score matching to control for prescription bias and potential confounders imbalance. RESULTS: Hazard ratio for death was reduced by 35% with radiotherapy and 24% with chemotherapy, compared to surgery alone. Combination therapy incorporating both modalities improved 5-yr survival (62.1%) compared to either treatment alone (51.4%). The sequencing of chemotherapy and radiotherapy or whether they were delivered as adjuvant vs. as neoadjuvant therapy did not affect their efficacy. Age>50years, tumor size>11cm, and tumor location on the trunk/pelvis were poor prognostic factors. CONCLUSION: Our analysis suggests that adjunctive modalities are both critical in the treatment of large high-grade ESTS, improving survival when used individually and demonstrating synergy in combination, regardless of sequencing relative to each other or relative to surgery; thus providing a framework for future randomized trials.

Customizable orthopaedic oncology implants: one institution's experience with meeting current IRB and FDA requirements.

BACKGROUND: Customizable orthopaedic implants are often needed for patients with primary malignant bone tumors due to unique anatomy or complex mechanical problems. Currently, obtaining customizable orthopaedic implants for orthopaedic oncology patients can be an arduous task involving submitting approval requests to the Institutional Review Board (IRB) and the Food and Drug Administration (FDA). There is great potential for the delay of a patient's surgery and unnecessary paperwork if the submission pathways are misunderstood or a streamlined protocol is not in place. PURPOSE: The objective of this study was to review the existing FDA custom implant approval pathways and to determine whether this process was improved with an institutional protocol. METHODS: An institutional protocol for obtaining IRB and FDA approval for customizable orthopaedic implants was established with the IRB at our institution in 2013. This protocol was approved by the IRB, such that new patients only require submission of a modification to the existing protocol with individualized patient information. During the two-year period of 2013-2014, eight patients were retrospectively identified as having required customizable implants for various orthopaedic oncology surgeries. The dates of request for IRB approval, request for FDA approval, and total time to surgery were recorded, along with the specific pathway utilized for FDA approval. RESULTS: The average patient age was 12 years old (7-21 years old). The average time to IRB approval of a modification to the pre-approved protocol was 14 days (7-21 days). Average time to FDA approval after submission of the IRB approval to the manufacturer was 12.5 days (7-19 days). FDA approval was obtained for all implants as compassionate use requests in accordance with Section 561 of the Federal Food Drug and Cosmetic Act's expanded access provisions. CONCLUSIONS: Establishment of an institutional protocol with pre-approval by the IRB can expedite the otherwise time-consuming and complicated process of obtaining customizable orthopaedic implants for orthopaedic oncology patients. LEVEL OF EVIDENCE: Retrospective case series, Level IV. See the Guidelines for authors for a complete description of levels of evidence.

Linea Aspera as Rotational Landmark for Tumor Endopostheses: A Computed Tomography Study.

This computed tomography study examined the reliability of the linea aspera as a rotational landmark in tumor endoprosthetic replacement by determining its cross-sectional location on the femur.

Results of 20 consecutive patients treated with the Repiphysis expandable prosthesis for primary malignant bone.

Limb-salvage for primary malignant bone tumors in pediatric patients presents a unique challenge when resection includes an active physis. Early expandable prostheses required open surgical procedures to achieve lengthening. Newer prostheses are capable of achieving expansion without open procedures through the use of an electromagnetic field. This study reports our results with 90 consecutive expansion procedures using the Repiphysis(®) prosthesis. We retrospectively reviewed the records of 20 patients (22 limbs) who underwent limb-salvage using the Repiphysis(®) prosthesis from 2003 to 2015. There were 9 males and 11 females with a mean age of 9 years and 9 months (6-16 years). Reconstruction included the distal femur in 11 cases, total femur in four, proximal tibia in three, proximal humerus in three, and total humerus in one. Complications were reviewed and functional scores were recorded using the MSTS/ISOLS system. Five patients had a second prosthesis implanted during the course of the study for a total of 27 prostheses. The mean follow-up was 57 (6-148) months. Four patients have not been expanded: three due to death prior to lengthening, and one patient who has not yet developed a leg length discrepancy. Ninety consecutive expansion procedures were performed in 18 limbs in 16 patients. A mean of 9 (5-20) mm was gained per expansion and 4.8 cm per patient who has undergone expansion to date. Seven patients have reached skeletal maturity and have been converted to an adult endoprosthesis. These patients averaged 8 expansions per patient and a mean of 7.4 (1.8-12.9) cm in length gained. There were 15 complications in 11 patients including one dislocation, one contracture, four cases of aseptic loosening, five structural failures (three expansion mechanism failures and two tibial fractures), three deep infections, and one case of local recurrence. The mean MSTS score was 80 % (37-97 %) and the limb retention rate was 95 %. The results of this study are comparable to previous studies involving non-invasive prostheses. This study hopefully provides additional data for clinicians to consider when faced with limb threatening sarcomas in the immature skeleton.

Oncoproteins and proliferation markers in synovial sarcomas: a clinicopathologic study of 19 cases.

PURPOSE: The objective of this study was to evaluate synovial sarcomas for the expression of oncogenic proteins (Her2/neu, EGFR, Bcl-2, p53) and proliferation markers (Ki-67, Topoisomerase 2alpha), as possible markers of prognostic significance. METHODS: From 17 patients with synovial sarcomas 19 tumors (15 primary, 2 recurrent, and 2 metastatic) were selected on the basis of characteristic histology, the expression of at least one epithelial marker, and/or the presence of t(X;18). Adequate follow-up was available in all cases. RESULTS: The tumors were tested immunohistochemically and were found to express multiple oncogenic proteins. Four of 19 synovial sarcomas (21%) demonstrated nuclear over-expression of p53 protein; 18 of 19 tumors (94%) stained positive for Bcl-2; and 13 of 19 tumors (68%) were immunoreactive with EGFR. Of particular interest was the frequent expression of Her2/neu, an oncogenic protein more commonly observed in epithelial neoplasms. Ten of 19 tumors (52%, 7 monophasic and 3 biphasic) showed positive cytoplasmic and membranous staining with Her2/neu (HercepTest, DAKO). The staining intensity ranged from 1+ to 2+. Cellular expression of Her2/neu was independent of EGFR positivity and showed no association with proliferative activity of the tumors. FISH analysis of eight positive cases showed no evidence of Her2/neu gene amplification. Among the non-metastatic tumors, we found a significant correlation between Ki-67 and Topoisomerase 2alpha. Spearman's correlation co-efficient was 0.86 with P=0.001 ( n=17). CONCLUSIONS: In this relatively small series of cases, we found no definite correlation between the over-expression of Her2/neu and clinical outcome. The over-expression of p53 was significantly associated with clinical outcome (Fisher's exact test, P=0.02).

Desmoplastic fibroma of the rib.

Desmoplastic fibroma is a very rare primary tumor of bone, closely related to aggressive fibromatosis of soft tissue. Although considered a benign lesion, it is locally destructive, can extend into the soft tissues, and has a high rate of local recurrences after incomplete surgical excision. Recognition of this entity is important to ensure proper surgical treatment. According to the published data, the tumor is most common in the long tubular bones (56%), the mandible (26%), and the pelvis (14%). Rib involvement by desmoplastic fibroma is extremely rare, and to our knowledge, only 3 cases have been reported in the literature to date. We present the case of a desmoplastic fibroma in the rib of a 19-year-old man, adding a fourth case to the previously reported cases involving this unusual location. The clinical history and the radiological and pathologic findings are presented.

Liquid-based vs. conventional smears in fine needle aspiration of bone and soft tissue tumors.

OBJECTIVE: To compare the accuracy of fine needle aspiration cytology of bone and soft tissue tumors utilizing ThinPrep (TP) (Cytyc Corporation, Boxborough, Massachusetts, U.S.A.) vs. conventional smears (CS). STUDY DESIGN: Fine needle aspiration cytology from bone and soft tissue tumors was processed and assessed for cellularity, nuclear and cytoplasmic preservation, cellular architecture and stromal background with both the TP liquid-based smear technique and conventional methods. RESULTS: An accurate diagnosis was made in 13% of TP cases as compared to 64% in CS cases. CONCLUSION: CS of fine needle aspiration sample is far superior to TP in diagnosing tumors of bone and soft tissues. Preservation of cytoplasmic features and cellular architecture was superior in conventionally prepared smears.