Limb Amputations in Cancer: Modern Perspectives, Outcomes, and Alternatives.

PURPOSE OF REVIEW: This review summarizes current findings regarding limb amputation within the context of cancer, especially in osteosarcomas and other bony malignancies. We seek to answer the question of how amputation is utilized in the contemporary management of cancer as well as explore current advances in limb-sparing techniques. RECENT FINDINGS: The latest research on amputation has been sparse given its extensive history and application. However, new research has shown that rotationplasty, osseointegration, targeted muscle reinnervation (TMR), and regenerative peripheral nerve interfaces (RPNI) can provide patients with better functional outcomes than traditional amputation. While limb-sparing surgeries are the mainstay for managing musculoskeletal malignancies, limb amputation is useful as a palliative technique or as a primary treatment modality for more complex cancers. Currently, rotationplasty and osseointegration have been valuable limb-sparing techniques with osseointegration continuing to develop in recent years. TMR and RPNI have also been of interest in the modern management of patients requiring full or partial amputations, allowing for better control over myoelectric prostheses.

Outcomes and Complications of Pelvic Chondrosarcomas Treated Using Navigation Guidance and Multidisciplinary Approach: Is the Tumor Volume a Prognostic Factor?

(1) Background: Pelvic Chondrosarcomas (CS) have a poor prognosis. The grade is the most important survival predictor; other factors are periacetabular location and Dedifferentiated CS subtype. The aim of the study is to investigate a series of CS of the pelvis, to analyze the prognostic factors that affect outcomes and to demonstrate how the use of intraoperative navigation can reduce the complications without worse outcomes. (2) Methods: Retrospective study on 35 patients (21 M, 14 F), median age at surgery 54 years (IQR 41−65), with pelvic CS, treated with hemipelvectomy under navigation guidance. (3) Results: 30 high-grade CS and 5 low-grade CS; mean follow-up 51.4 months. There was a positive linear correlation between the tumor volume and the presence of local recurrence at follow-up. The mean survival time of patients with larger chondrosarcoma volume was lower, but not significantly so. Lower MSTS score was associated with significantly lower survival time (p < 0.001). (4) Conclusion: in this series overall survival, LR and distant metastasis were comparable with recent literature, while complication rate was lower compared to similar series without the use of navigation. There was a correlation between tumor volume and local recurrence rate but not with the presence of metastasis at follow up.

Phase III Trial Adding Vincristine-Topotecan-Cyclophosphamide to the Initial Treatment of Patients With Nonmetastatic Ewing Sarcoma: A Children's Oncology Group Report.

PURPOSE: The primary aim of this phase III randomized trial was to test whether the addition of vincristine, topotecan, and cyclophosphamide (VTC) to interval compressed chemotherapy improved survival outcomes for patients with previously untreated nonmetastatic Ewing sarcoma. METHODS: Patients were randomly assigned to receive standard five-drug interval compressed chemotherapy (regimen A) for 17 cycles or experimental therapy with five cycles of VTC within the 17 cycles (regimen B). Patients were stratified by age at diagnosis (< 18 years and ≥18 years) and tumor site (pelvic bone, nonpelvic bone, and extraosseous). Tumor volume at diagnosis was categorized as < 200 mL or ≥ 200 mL. Local control occurred following six cycles. Histologic response was categorized as no viable or any viable tumor. Event-free survival (EFS) and overall survival (OS) were compared between randomized groups with stratified log-rank tests. RESULTS: Of 642 enrolled patients, 309 eligible patients received standard and 320 received experimental therapy. The 5-year EFS and OS were 78% and 87%, respectively. There was no difference in survival outcomes between randomized groups (5-year EFS regimen A v regimen B, 78% v 79%; P = .192; 5-year OS 86% v 88%; P = .159). Age and primary site did not affect the risk of an EFS event. However, age ≥ 18 years was associated with an increased risk of death at 5 years (hazard ratio 1.84; 95% CI, 1.15 to 2.96; P = .009). The 5-year EFS rates for patients with pelvic, nonpelvic bone, and extraosseous primary tumors were 75%, 78%, and 85%, respectively. Tumor volume ≥ 200 mL was significantly associated with lower EFS. CONCLUSION: While VTC added to five-drug interval compressed chemotherapy did not improve survival, these outcomes represent the best survival estimates to date for patients with previously untreated nonmetastatic Ewing sarcoma.

Osteosarcoma: An Evolving Understanding of a Complex Disease.

Osteosarcoma is the most common primary bone sarcoma and affects both children and adults. The cornerstone of treatment for patients with localized and oligometastatic disease remains neoadjuvant chemotherapy, surgical resection of all sites of disease, followed by adjuvant chemotherapy. This approach is associated with up to an 80% 5-year survival. However, survival of patients with metastatic disease remains poor, and overall, osteosarcoma remains a challenging disease to treat. Advances in the understanding of molecular drivers of the disease, identification of poor prognostic factors, development of risk-stratified treatment protocols, successful completion of large collaborative trials, and surgical advances have laid the ground work for progress. Advances in computer navigation, implant design, and surgical techniques have allowed surgeons to improve patients' physical functional without sacrificing oncologic outcomes. Future goals include identifying effective risk stratification algorithms which minimize patient toxicity while maximizing oncologic outcomes and continuing to improve the durability, function, and patient acceptance of oncologic reconstructions.

Budget Impact of Adaptive Abiraterone Therapy for Castration-Resistant Prostate Cancer.

BACKGROUND: The use of a novel strategy known as adaptive abiraterone therapy based on mathematical modeling of evolutionary dynamics of tumor subpopulations was shown in a clinical trial to extend the time to disease progression in patients with metastatic castration-resistant prostate cancer (CRPC) and reduced the use of abiraterone therapy. Although the clinical impact of adaptive abiraterone treatment is clear, the economic impact of this strategy has not been investigated. OBJECTIVE: To compare the cost of care with adaptive abiraterone therapy versus standard continuous abiraterone therapy in patients with metastatic CRPC, using patient billing data. METHODS: We performed a retrospective review of billing data for patients with metastatic CRPC who received abiraterone treatment at a large cancer center between June 1, 2012, and August 31, 2018. Patients were divided into 2 groups based on whether they received adaptive abiraterone therapy (N = 15) or continuous abiraterone therapy (N = 21). All patients with refractory, metastatic prostate cancer after castration that was indicated for abiraterone therapy were eligible for this study. Each patient in the adaptive abiraterone therapy cohort received abiraterone plus prednisone treatment until the patient reached a target threshold of 50% or more reduction in prostate-specific antigen (PSA) level compared with his PSA level before abiraterone therapy; treatment was then suspended until the PSA level rose above the 50% of PSA before abiraterone therapy target threshold. The continuous therapy cohort received abiraterone plus prednisone daily until radiographic progression. The primary outcomes were the mean annual cost of care per patient, including and excluding the cost of abiraterone, and the cost of care, by clinical category. RESULTS: The median time to disease progression was 25.8 months for patients who received adaptive abiraterone therapy compared with 12.1 months for patients who received continuous abiraterone therapy. Overall, the mean total, including the cost of drug, annual cost per patient who received adaptive abiraterone therapy was $79,093 compared with $146,782 for patients who received continuous abiraterone therapy (P <.0001). The annual cost of care per patient, excluding the cost of abiraterone, was $13,883 for those who received adaptive therapy versus $22,322 for those who received continuous abiraterone therapy (P = .2757), which was not statistically significant. CONCLUSION: Practical precision medicine strategies, such as adaptive abiraterone treatment or pharmacogenomics-targeted dosing, can use known biomarkers, such as PSA, to tailor therapy, generate improved outcomes, and reduce costs without the need for novel drug and diagnostic discovery and development. The results of this study suggest that a large clinical study of adaptive abiraterone therapy is warranted to validate the potential of this strategy to extend the time to disease progression and reduce costs of treatment of metastatic CRPC.

Intraoperative Localization Using an Implanted Radar Reflector Facilitates Resection of Non-Palpable Trunk and Extremity Sarcoma.

BACKGROUND: Resecting non-palpable soft tissue tumors presents a unique challenge, particularly with recurrent disease in which surrounding tissue has been surgically manipulated and often irradiated. SAVI SCOUT® is a radar-based localization device that was developed for breast tumor localization and was recently FDA-approved for localization of soft tissue tumors. Application of this technology to soft tissue sarcoma has not been previously reported. METHODS: We assembled a single-institution retrospective case series of patients with trunk and extremity sarcomas resected by five sarcoma surgeons using SAVI SCOUT® from December 2018 to May 2020. Reflectors were placed preoperatively using image-guidance, and the radar detector was used intraoperatively to localize the target lesion. Clinical variables were abstracted from the electronic medical record including treatment history, pathology, and early oncologic outcomes. Using a focused review, we compared margin status and recurrence rates with previously published cohorts. RESULTS: Ten SAVI SCOUT®-localized sarcoma resections were performed. Eight were for locally recurrent disease, of which seven (83%) had prior radiation. The remaining lesions became non-palpable after neoadjuvant chemotherapy. SAVI SCOUT® facilitated resection in all cases with a margin-negative resection rate (77%) comparable to prior cohorts. In this high-risk population with a median follow-up of 14 months, only one patient recurred locally 7.5 months after SAVI SCOUT®-localized resection, requiring re-resection. CONCLUSION: SAVI SCOUT® technology facilitated resection of non-palpable recurrent sarcoma of the trunk and extremities in all ten cases attempted. In a high-risk patient population, the pattern of recurrence has been primarily distant with one instance of local tumor recurrence.

Malignancy in giant cell tumor of bone in the extremities.

BACKGROUND: Malignancy in giant cell tumor of bone (GCTB) is a rare tumor with relevant literature being sparse. In primary malignant GCTB, distinct areas of benign GCTB are juxtaposed with high-grade sarcoma, while in secondary malignant GCTB sarcoma occurs at the site of previously managed GCTB. This study assesses the distinguishing characteristics of patients with this condition, the time interval for development of secondary malignant GCTB, the outcome of treatment, and explores factors associated with oncologic outcomes. METHODS: This is a retrospective case series of patients from a prospectively collected institutional musculoskeletal oncology database. From January 1998 to December 2016, 1365 patients were managed for extremity GCTBs. 32 (2.3%) patients had malignant GCTB, including 12 with primary malignant GCTB and 20 with secondary malignant GCTB. The study population comprised 18 males and 14 females presenting at a mean age of 33.7 years (±13.0) and followed for a mean of 9.5 years (±7.4). Data were collected on patient and treatment-related factors, and the occurrence of local recurrence, metastasis, and death. The time from the diagnosis of GCTB to the secondary malignant GCTB was defined as the latent period. RESULTS: Malignant GCTB most commonly presents in the distal femur and proximal tibia with pain and swelling. Radiologically, they are aggressive Campanacci Grade III tumors with prominent bony destruction and soft tissue extension. In the 20 patients with secondary malignant GCTB, the tumors were osteosarcoma in 15, undifferentiated pleomorphic sarcoma in 4 patients and fibrosarcoma in one patient. The mean latent period in patients with secondary malignant GCTB was 7.9 year (±7.3). The median recurrence-free survival (RFS) of secondary malignant GCTB (latent period) and benign GCTB were 61.5 and 19 months respectively (p < 0.001), receiver operating curve analysis found 49.5 months to be the critical threshold, with a longer interval to recurrence being seen in malignant recurrence. The 5 and 10-year overall survival rate of malignant GCTB were 45.8% and 36.1% respectively. The 5-year survival rates of primary malignant GCTB and secondary malignant GCTB were 56.2% and 40.0% respectively (p = 0.188). Adequate surgical margins decreased the local recurrence (LR) rate (P = 0.006). Pulmonary metastasis developed in 69% of patients. The median distant metastasis-free survival between malignant GCTB and benign GCTB were 9 and 21 months (p = 0.002). Chemotherapy was associated with a longer pulmonary metastasis free survival (13 months Vs 6 months, P = 0.002), but not with increased overall survival (57.0% Vs 33.3%, P = 0.167). CONCLUSIONS: Malignant GCTB carries a poor prognosis. Accurate diagnosis is critical to avoid inadequate surgical margins when treating primary malignant GCTB. Aggressive tumors and pulmonary metastasis should raise suspicion for malignant GCTB. Secondary malignant transformation should be suspected in patients presenting with recurrence especially after 4 years. Adjuvant chemotherapy use did not benefit survival, but was associated with increased pulmonary progression-free survival.

Nonmechanical Revision Indications Portend Repeat Limb-Salvage Failure Following Total Femoral Replacement.

BACKGROUND: There is scant evidence to guide decision-making for patients considering total femoral replacement (TFR). We aimed to identify the indication, patient, disease, and surgical technique-related factors associated with failure. We hypothesized that failure occurs more frequently in the setting of revision surgical procedures, with infection as the predominant failure mode. METHODS: We performed a retrospective cohort study of patients receiving total femoral endoprostheses for oncological and revision arthroplasty indications; 166 patients met these criteria. Our primary independent variable of interest was TFR for a revision indication (arthroplasty or limb salvage); the primary outcome was failure. Analyses were performed for patient variables (age, sex, diagnosis group, indication), implant variables (model, decade, length, materials), and treatment variables. We analyzed TFR failures with respect to patient factors, operative technique, and time to failure. We conducted bivariate logistic regressions predicting failure and used a multivariate model containing variables showing bivariate associations with failure. RESULTS: Forty-four patients (27%) had treatment failure. Failure occurred in 24 (23%) of 105 primary TFRs and in 20 (33%) of 61 revision TFRs; the difference was not significant (p = 0.134) in bivariate analysis but was significant (p = 0.044) in multivariate analysis. The mean age at the time of TFR was 37 years in the primary group and 51 years in the revision group (p = 0.0006). Of the patients who had mechanical failure, none had reoccurrence of their original failure mode, whereas all 8 patients from the nonmechanical cohort had reoccurrence of the original failure mode; this difference was significant (p = 0.0001). CONCLUSIONS: TFR has a high failure rate and a propensity for deep infection, especially in the setting of revision indications and prior infection. All failed TFRs performed for revision indications for infection or local recurrence failed by reoccurrence of the original failure mode and resulted in amputation. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Clinical Utility of Genomic Profiling in the Treatment of Advanced Sarcomas: A Single-Center Experience.

PURPOSE: Sarcomas are a diverse group of malignant tumors that arise from soft tissues or bone. For most advanced cases, there is a substantial need for improved therapeutic options and, therefore, a desire to more precisely tailor therapy in individual cases. In this study, we review our institutional experience with next-generation sequencing (NGS)-based molecular profiling for non-GI stromal tumors sarcomas, with a focus on the clinical utility of the results. PATIENTS AND METHODS: We retrospectively analyzed results of NGS performed on tumors from 114 patients with a diagnosis of sarcoma. A chart review was conducted to review the clinical impact of NGS findings. RESULTS: A median of three putatively oncogenic gene alterations were identified per tumor sample (range, 0 to 19) and at least one mutation was detected in 96.7% of tumors. Fifty-six patients (49.1%) harbored a finding that was felt to be actionable after review by a molecular tumor board. Five patients (4.4%) had a diagnosis change as a result of NGS findings. In 15 patients (13.2%), therapeutic selection was influenced by NGS findings. Four of 15 (26.7%) of the NGS-influenced systemic therapies resulted in clinical benefit. CONCLUSION: Putatively oncogenic mutations are readily detected in the majority of sarcomas. Genetic profiling affected the diagnosis and/or treatment approach in a sizeable minority of patients with sarcoma treated at our center. Additional study is required to determine if genetic profiling leads to improved clinical outcomes.

Percutaneous Acetabuloplasty for Metastatic Lesions to the Pelvis.

Metastatic lesions of the acetabulum can be painful and debilitating. First-line treatment is multimodal and consists of disease-specific chemotherapy, osteoclastic inhibitors, analgesics, and radiation therapy. When these therapies fail, surgical intervention usually is indicated and varies from regional defect stabilization to large periacetabular reconstructions that are demanding procedures with high rates of complications. Percutaneous cement augmentation (acetabuloplasty) of lesions in selected patients has been explored as a less invasive method of lesional control. This retrospective review included 11 patients with painful periacetabular lesions who underwent percutaneous acetabuloplasty using fluoroscopic guidance from 2007 to 2012, in addition to standard treatment with either radiation or chemotherapy, or a combination of both radiation and chemotherapy. Primary tumors included 4 multiple myeloma, 4 renal cell, and 3 breast malignancies. Mean procedure length was 58.4 minutes, and mean hospital stay was 1.4 days (range, 1-2 days). Mean blood loss was 33.4 mL, and there were no complications due to infection or cementation. Mean follow-up was 26.4 months (range, 3-36 months), with 2 patients dying from complications of underlying disease. All of the patients experienced pain relief following the procedure, with mean visual analog scale scores improving from 7.7 to 2.1 (P=.002). Postoperative Musculoskeletal Tumor Society and Oxford hip scores were obtained for 7 of 11 patients and demonstrated improvement. One patient underwent conversion to an acetabular reconstruction due to disease progression. This report demonstrates the effective use of a minimally invasive procedure to provide acute stability, pain relief, and good functional outcomes in patients with periacetabular metastatic lesions without pathologic fracture. [Orthopedics. 2017; 40(1):e170-e175.].

Radiologic Approach to Bone and Soft Tissue Sarcomas.

Diagnostic imaging plays an important role in evaluation and treatment planning of patients with musculoskeletal tumors. This article discusses various imaging modalities available in the work-up, staging, and surveillance of patients with primary bone and soft tissue neoplasms. A systematic approach to initial evaluation of newly suspected bone lesions and soft tissue masses is presented. Reviewed are relevant imaging features of musculoskeletal neoplasms that help predict tumor biology and risk of malignancy and findings that define internal tumor composition and allow for accurate preoperative histopathologic diagnosis before intervention. Finally, the role of diagnostic imaging in tumor staging, evaluation of response to neoadjuvant therapy, and postoperative surveillance is discussed.

Surgical and Functional Outcomes After Limb-Preservation Surgery for Tumor in Pediatric Patients: A Systematic Review.

BACKGROUND: Limb-salvage surgery and segmental reconstruction for the treatment of lower extremity osseous tumors in the pediatric population have been described in the literature, but there is little consensus regarding the optimal surgical treatment for this patient population. METHODS: A systematic review of the literature was performed to identify studies focusing on limb-salvage procedures in pediatric patients who were managed with one of three reconstructions with use of a metallic endoprosthesis, allograft, or allograft-prosthesis composite. Data were segregated according to the excised and reconstructed anatomical location (proximal part of the femur, total femur, distal part of the femur, proximal part of the tibia) and were collated to assess modes of failure and functional outcomes of each reconstruction type for each anatomic location. RESULTS: Sixty articles met the inclusion criteria; all were Level-IV evidence, primarily consisting of small, retrospective case series. Infection was a primary mode of failure across all reconstruction types and locations, whereas allograft reconstructions were susceptible to structural failure as well. The rate of failure in the pediatric population correlated well with previously published results for adults. The incidence of subsequent amputation was lower in the pediatric population (5.2%) than has been reported in adults (9.5%) (p = 0.013). Meaningful growth of expandable metallic endoprostheses was reported in the literature, with an overall rate of leg-length discrepancy of 13.4% being noted at the time of the latest follow-up. The Musculoskeletal Tumor Society (MSTS) questionnaire was the most consistently used outcome measure in the literature, with average scores ranging from 71.0% to 86.8%, depending on reconstruction type and anatomic location. CONCLUSIONS: The current state of the literature detailing the surgical and functional outcomes of segmental reconstruction for the treatment of pediatric bone tumors is limited to Level-IV evidence and is complicated by under-segregation of the data by age and anatomical location of the reconstruction. Despite these limitations, pediatric limb-salvage surgery demonstrates satisfactory initial surgical and functional outcomes. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

A Modified Lodwick-Madewell Grading System for the Evaluation of Lytic Bone Lesions.

OBJECTIVE: Lodwick's well-established grading system of lytic bone lesions has been widely used in predicting growth rate for lytic bone lesions. We applied a Modified Lodwick-Madewell Grading System as an alternative means to categorize lytic bone tumors into those with low, moderate, and high risks of malignancy. MATERIALS AND METHODS: A retrospective review of the radiographs of 183 bone lesions was performed. Cases were selected to include a broad range of benign and malignant tumors. Readers applied our Modified Lodwick-Madewell Grading System, and consensus was reached in all cases. This modified system consists of grade I, which is composed of grades IA and IB as listed in the Lodwick system; grade II, which is grade IC in the Lodwick system; and grade III, which is composed of IIIA (changing margination), IIB (moth-eaten and permeative patterns), and IIIC (radiographically occult). Grading was correlated with the final diagnosis. RESULTS: Of the 183 tumors, 81 were classified as grade I, 54 as grade II, and 48 as grade III. When correlating grade with pathology, we found that 76 of 81 (94%) grade I lesions were benign and 39 of 48 grade III lesions (81%) were malignant. A nearly equal number of grade II lesions proved to be benign (29/54; 54%) and malignant (28/54; 53%). CONCLUSION: By expanding Lodwick's grading system to include two additional patterns of disease described by Madewell and colleagues (changing margination and radiographically occult) and by reclassifying them into three distinct grades, we propose a modified system-the Modified Lodwick-Madewell Grading System. Application of this system shows correlation of tumor grade with tumor biologic activity and with risk of malignancy: Grade I lesions are usually benign, grade II lesions carry moderate risk of malignancy, and grade III lesions possess a high likelihood of malignancy.

Do Surgical Margins Affect Local Recurrence and Survival in Extremity, Nonmetastatic, High-grade Osteosarcoma?

BACKGROUND: Long-term survival for all patients with osteosarcoma using current aggressive adjuvant chemotherapy and surgical resection is between 60% and 70%. In patients who present with nonmetastatic, high-grade extremity osteosarcoma of bone, limb salvage surgery is favored, when appropriate, over amputation to preserve the limb, because limb salvage may lead to a superior quality of life compared with amputation. However, concern remains that in the attempt to preserve the limb, close or microscopically positive surgical margins may have an adverse effect on event-free survival. QUESTIONS/PURPOSES: (1) Does a positive or close surgical margin increase the likelihood of a local recurrence? (2) Does a positive or close surgical margin adversely affect the development of metastatic disease? (3) What is the relationship of surgical margin on overall survival? METHODS: With institutional review board approval, we retrospectively evaluated 241 patients treated at our institution between 1999 and 2011. Exclusion criteria included nonextremity locations, metastatic disease at initial presentation, low- or intermediate-grade osteosarcoma, treatment regimens that did not follow National Comprehensive Cancer Network (NCCN) guidelines, incomplete medical records, and any part of treatment performed outside of Moffitt Cancer Center or All Children's Hospital. Fifty-one patients were included in the final analysis, of whom 31 (61%) had followup data at a minimum of 2 years or whose clinical status was known but had died before 2 years of followup. Margin status was defined as (1) microscopically positive; (2) negative ≤ 1 mm; and (3) negative > 1 mm. Margin status, histologic response (tumor percent necrosis), type of osteosarcoma, type of surgery, presence of local recurrence, metastatic disease, and overall survival were recorded for each patient. The mean age was 22 years (range, 12-74 years) and the mean followup was 3 years (range, 0.1-14 years). Margin status was positive in 10% (five of 51), negative ≤ 1 mm 26% (13 of 51), and negative > 1 mm 65% (33 of 51). RESULTS: Local recurrence was noted to be 14% (seven of 51) at 3.4 years. After controlling for relevant confounding variables, the presence of a positive margin compared with a negative margin > 1 mm was the only independent predictor of local recurrence (hazard ratio [HR], 8.006; 95% confidence interval [CI], 1.314-48.781; p = 0.0241). At a mean of 3.4 years, 29% (15 of 51) of the patients developed metastatic disease with no difference with the numbers available in the probability of developing metastatic disease among the three margin groups (p = 0.614). Overall survival at 3.8 years was 75% (38 of 51). After controlling for relevant confounding variables, we found that patients with positive margins were more likely to die from disease than those with negative margins (HR, 6.26; 95% CI, 1.50-26.14; p = 0.0119); no other independent predictors of survival were identified. CONCLUSIONS: With the numbers of patients we had, we observed that patients with extremity, nonmetastatic, high-grade osteosarcoma who had positive margins showed a higher probability of local recurrence in comparison to those with negative surgical margins. Given that positive margins appear to be associated with poorer survival in patients with high-grade osteosarcoma of the extremities, surgeons should strive to achieve negative margins, but larger studies are needed to confirm these findings. LEVEL OF EVIDENCE: Level III, therapeutic study.

Clinical Characteristics and Outcomes for Solitary Fibrous Tumor (SFT): A Single Center Experience.

Solitary fibrous tumor (SFT) is a mesenchymal neoplasm of fibrous origin. The 2013 WHO classification of soft tissue tumors defines malignant forms as hypercellular, mitotically active (>4 mitosis/10 high-power fields), with cytological atypia, tumor necrosis, and/or infiltrative margins. With an IRB-approved protocol, we investigated patient records and clinicopathologic data from our Sarcoma Database to describe the clinical characteristics of both benign and malignant SFT. All pathology specimens were reviewed by two pathologists. Descriptive statistics and univariate/multivariate survival analysis were performed. Patient records and Social Security Death Index were used to evaluate vital status. Of 82 patients, 47 (57%) were women and 73 (89%) were Caucasian. Median age was 62 years (range, 20 to 89). Thirty-two (39%) patients succumbed to the disease. Primary tumor site was lung/pleura in 28 (34%), abdomen/pelvis in 23 (28%), extremity in 13 (16%), and head/neck in 9 (11%) patients. Pathology was described as benign in 42 (51%) and malignant in 40 (49%) patients. Compared to benign SFT, malignant histology is associated with larger tumor size, higher mitotic counts, metastatic disease at diagnosis, and greater use of chemotherapy and radiation therapy. Gender, age, and tumor site were not significantly different between benign and malignant subtypes. By univariate analysis, only benign vs. malignant variant and complete resection positively impacted overall survival (P = 0.02 and P<0.0001, respectively). In the multivariable analysis of overall survival, receiving chemotherapy or not receiving surgery were two variables significantly associated with higher failure rate in overall survival: patients with chemotherapy vs. no chemotherapy (P = 0.003, HR = 4.55, with 95% CI: 1.68-12.34) and patients without surgery vs. with surgery (P = 0.005, HR = 25.49, with 95% CI: 2.62-247.57). Clear survival differences exist between benign and malignant SFT. While surgery appears to be the best treatment option for benign and malignant SFT, better systemic therapies are needed to improve outcomes of patients with metastatic, malignant SFT.

Expandable Total Humeral Replacement in a Child with Osteosarcoma.

Case. A right-handed 8-year-old female patient presented with a conventional, high-grade osteosarcoma involving her right humerus; through-shoulder amputation was recommended. After consultation, total humerus resection with expandable, total humeral endoprosthesis reconstruction was performed with a sleeve to encourage soft-tissue ingrowth. At three-year follow-up she has received one lengthening procedure and her functional scores are excellent. Conclusion. Total humeral resection and replacement in the pediatric population are rare and although early reports of expandable total humeral endoprosthesis outcomes demonstrate high failure rates, this patient's success indicates that expandable total humeral replacement is a viable option.

Chondroblastoma of bone in the extremities: a multicenter retrospective study.

BACKGROUND: Chondroblastoma is a rare benign cartilage tumor that commonly occurs in children and adolescents. This study was designed to review the epidemiologic characteristics and outcomes of surgical management in a large series of patients with extremity chondroblastoma. METHODS: We performed a multicenter retrospective analysis of 199 patients with extremity chondroblastoma. Clinical data, radiographic images, histological findings, treatment, and outcome were analyzed. RESULTS: There were 145 male patients and fifty-four female patients with a mean age of 18.0 years. The most commonly involved bone was the proximal part of the tibia (fifty-five patients [27.6%]), followed by the proximal part of the femur (fifty-two patients [26.1%]) and the distal part of the femur (thirty-eight patients [19.1%]). Prior to presentation, 73.4% (146 of 199 patients) experienced pain. The mean duration of pain and other symptoms was 8.7 months. The physis was open in 25.7%, it was closing in 22.2%, and it was closed in 52.1% of the patients at the time of presentation. One hundred and twenty-six patients had at least twenty-four months of follow-up; their mean follow-up duration was 62.1 months (range, twenty-four to 190 months). Initial treatment was curettage for 119 patients (94.4%) and en bloc resection for seven patients (5.6%). The local recurrence rate was 5.0% after curettage and 0% after resection. The only significant factor related to recurrence was the location of the lesion in the proximal part of the humerus (p = 0.001). CONCLUSIONS: Chondroblastoma occurs most frequently in the proximal part of the tibia and the proximal part of the femur with significant male predilection. In this series, recurrence was most frequent in the proximal part of the humerus. Our results suggest that curettage and bone-grafting provide favorable local control and satisfactory functional outcome for patients with this disease. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Methotrexate, Doxorubicin, and Cisplatin (MAP) Plus Maintenance Pegylated Interferon Alfa-2b Versus MAP Alone in Patients With Resectable High-Grade Osteosarcoma and Good Histologic Response to Preoperative MAP: First Results of the EURAMOS-1 Good Response Randomized Controlled Trial.

PURPOSE: EURAMOS-1, an international randomized controlled trial, investigated maintenance therapy with pegylated interferon alfa-2b (IFN-α-2b) in patients whose osteosarcoma showed good histologic response (good response) to induction chemotherapy. PATIENTS AND METHODS: At diagnosis, patients age ≤ 40 years with resectable high-grade osteosarcoma were registered. Eligibility after surgery for good response random assignment included ≥ two cycles of preoperative MAP (methotrexate, doxorubicin, and cisplatin), macroscopically complete surgery of primary tumor, < 10% viable tumor, and no disease progression. These patients were randomly assigned to four additional cycles MAP with or without IFN-α-2b (0.5 to 1.0 µg/kg per week subcutaneously, after chemotherapy until 2 years postregistration). Outcome measures were event-free survival (EFS; primary) and overall survival and toxicity (secondary). RESULTS: Good response was reported in 1,041 of 2,260 registered patients; 716 consented to random assignment (MAP, n = 359; MAP plus IFN-α-2b, n = 357), with baseline characteristics balanced by arm. A total of 271 of 357 started IFN-α-2b; 105 stopped early, and 38 continued to receive treatment at data freeze. Refusal and toxicity were the main reasons for never starting IFN-α-2b and for stopping prematurely, respectively. Median IFN-α-2b duration, if started, was 67 weeks. A total of 133 of 268 patients who started IFN-α-2b and provided toxicity information reported grade ≥ 3 toxicity during IFN-α-2b treatment. With median follow-up of 44 months, 3-year EFS for all 716 randomly assigned patients was 76% (95% CI, 72% to 79%); 174 EFS events were reported (MAP, n = 93; MAP plus IFN-α-2b, n = 81). Hazard ratio was 0.83 (95% CI, 0.61 to 1.12; P = .214) from an adjusted Cox model. CONCLUSION: At the preplanned analysis time, MAP plus IFN-α-2b was not statistically different from MAP alone. A considerable proportion of patients never started IFN-α-2b or stopped prematurely. Long-term follow-up for events and survival continues.