Lawrence R. Menendez

A Meta-Analysis of Osteosarcoma Outcomes in the Modern Medical Era

Four decades ago, specialized chemotherapy regimens turned osteosarcoma, once considered a uniformly fatal disease, into a disease in which a majority of patients survive. Though significant survival gains were made from the 1960s to the 1980s, further outcome improvements appear to have plateaued. This study aims to comprehensively review all significant, published data regarding osteosarcoma and outcome in the modern medical era in order to gauge treatment progress. Our results indicate that published survival improved dramatically from 1960s to 1980s and then leveled, or in some measures decreased. Recurrence rates decreased in the 1970s and then leveled. In contrast, published limb salvage rates have increased significantly every recent decade until the present. Though significant gains have been made in the past, no improvement in published osteosarcoma survival has been seen since 1980, highlighting the importance of a new strategy in the systemic management of this still very lethal condition.

Survivorship and clinical outcome of modular endoprosthetic reconstruction for neoplastic disease of the lower limb

We reviewed retrospectively the results in 211 consecutive patients who had undergone limb salvage for bone neoplasia with endoprosthetic reconstruction of the proximal femur (96), distal femur (78), proximal tibia (30) and total femur (7). Their mean age was 50 years (11 to 86) and the mean follow-up period was 37.3 months (1 to 204). A total of 35 (16.6%) prostheses failed. Overall, implant survival was 78% (95% confidence interval (CI) 0.29 to 0.54) at five years, 60% (95% CI 0.93 to 2.35) at ten years and 60% (95% CI 1.27 to 3.88) at 15 years. Survivorship of the limb was 97.6% (95% CI 1.73 to 3.35) at ten years. The gender, age, diagnosis and location of the tumour were not prognostic variables for failure. Modular endoprosthetic replacement in the lower limb is a durable long-term reconstructive option, with the implants generally outlasting the patient.

Thermal Ablation of Osteoid Osteoma: Overview and Step-by-Step Guide

Osteoid osteoma is a small, benign but painful lesion with specific clinical and imaging characteristics. Computed tomography is the imaging modality of choice for visualization of the nidus and for treatment planning. Complete surgical excision of the nidus is curative, providing symptomatic relief, and is the traditionally preferred treatment. However, surgery has disadvantages, including the difficulty of locating the lesion intraoperatively, the need for prolonged hospitalization, and the possibility of postoperative complications ranging from an unsatisfactory cosmetic result to a fracture. Percutaneous radiofrequency (RF) ablation, which involves the use of thermal coagulation to induce necrosis in the lesion, is a minimally invasive alternative to surgical treatment of osteoid osteoma. With reported success rates approaching 90%, RF ablation should be considered among the primary options available for treating this condition.

A Comparison of Fine-needle Aspiration, Core Biopsy, and Surgical Biopsy in the Diagnosis of Extremity Soft Tissue Masses

BackgroundBiopsy tissue can be obtained through a fine needle, a wider coring needle, or through an open surgical incision. Though much literature exists regarding the diagnostic yield of these techniques individually, none compare accuracy of diagnosis in the same mass.Questions/purposesWe asked how the diagnostic accuracy of fine-needle aspiration, core biopsy, and open surgical biopsy compare in regard to identifying malignancy, establishing the exact diagnosis, and guiding the appropriate treatment of soft tissue masses.Patients and MethodsWe prospectively studied 57 patients with palpable extremity soft tissue masses, performing fine-needle aspiration, followed by core biopsy, followed by surgical biopsy of the same mass.ResultsOpen surgical biopsy was 100% accurate on all accounts. With regard to determining malignancy, fine-needle aspiration and core biopsy had 79.17% and 79.2% sensitivity, 72.7% and 81.8% specificity, 67.9% and 76% positive predictive value, 82.8% and 84.4% negative predictive value, and an overall accuracy of 75.4% and 80.7%, respectively. In regard to determining exact diagnosis, fine-needle aspiration had a 33.3% accuracy and core biopsy had a 45.6% accuracy. With regard to eventual treatment, fine-needle aspiration was 38.6% accurate and core biopsy was 49.1% accurate.ConclusionsIn soft tissue mass diagnosis, core biopsy is more accurate than fine-needle aspiration on all accounts, and open biopsy is more accurate than both in determining malignancy, establishing the exact diagnosis, and the guiding appropriate treatment.Level of Evidence Level I, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence.

Endoprosthetic reconstruction for neoplasms of the proximal femur

Limb salvage has become an important alternative to amputation in the treatment of bone neoplasms. We sought to determine whether the survivorship of modular proximal femur endoprostheses compares to that of custom implants and if specified factors predict failure. We additionally assessed the intermediate clinical and functional results with regard to complications and outcome. We retrospectively reviewed 96 consecutive patients who underwent endoprosthetic reconstruction for neoplastic disease and assessed patient, implant, and limb survivorship. The mean patient age was 59 years (range, 14-86 years). The average duration of followup was 18.1 months (range, 1-129 months). Nine (9.3%) prostheses failed and the rate of revision was 7.3% (7/96). Overall implant survival was 82% at 5 years and 10 years. Survivorship of the limb was 99% at 5 years. Patients in whom the articulating head segment was a total hip had a higher rate of revision compared with those who had undergone bipolar replacement. The mean MSTS score was 22 points (range, 15-25 points). Modular endoprosthetic replacement of the proximal femur is a durable reconstructive option and implants will generally outlive the patient with neoplastic disease. Bipolar head segments should be used whenever possible because of increased survival and decreased rates of dislocation.Level of Evidence: Therapeutic study, level IV (case series). See the Guidelines for Authors for a complete description of levels of evidence.

Intercalary endoprosthetic reconstruction for diaphyseal bone tumours

Custom-made intercalary endoprostheses may be used for the reconstruction of diaphyseal defects following the resection of bone tumours. The aim of this study was to determine the survival of intercalary endoprostheses with a lap joint design, and to evaluate the clinical results, complications and functional outcome. We retrospectively reviewed six consecutive patients, three of whom underwent limb salvage with intercalary endoprostheses of the tibia, two of the femur, and one of the humerus. Their mean age was 42 years (28 to 64). The mean follow-up was 21.6 months (9 to 58). The humeral prosthesis required revision at 14 months owing to aseptic loosening. There were no implant-related failures. Musculoskeletal Tumour Society functional outcome scores indicated that patients achieved 90% of premorbid function. Custom intercalary endoprostheses result in reconstructions comparable with, if not better than, those of allografts. Using this design of implant reduces the incidence of early complications and difficulties experienced with previous versions.

Influence of cryosurgery on treatment outcome of low-grade chondrosarcoma

Successfully managing low-grade chondrosarcomas with margins considered less than wide would minimize the need for extensive reconstruction. We report our experience using cryotherapy as an adjuvant to treat patients with low-grade intracompartmental chondrosarcomas. Ten consecutive patients had intralesional resections including curettage, cryo-surgery, and polymethylmethacrylate application. Eight of these patients required prophylactic skeletal stabilization. We retrospectively reviewed the outcomes for tumor recurrence, disease progression, and complications. The Musculo-skeletal Tumor Society rating scale was used to evaluate functional outcome, and the mean score was 27 points (range, 25-30 points). The mean age of the patients was 54.4 years (range, 29-83 years), and the average followup was 38.5 months (range, 24-60 months). Patients were treated for lesions of the femur (n = 3), humerus (n = 3), scapula (n = 2), tibia (n = 1), and acetabulum (n = 1). There was no evidence of recurrence or metastases. At the latest followup, all patients were well, however, one patient had hardware loosening. In this small group of patients, intralesional resection with adjuvant cryoablation provided an alternative to more radical procedures for low-grade intracompartmental chondrosarcoma.Level of Evidence: Level IV Therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

F-18 FDG PET and PET/CT evaluation of response to chemotherapy in bone and soft tissue sarcomas.

Objective: F-18 FDG PET has been used to grade sarcomas and assess response to therapy in advanced disease. Certain chemotherapy agents are thought to induce an inflammatory response in the tumor bed that can make interpretation of post-therapy FDG PET scans difficult. A review of our experience with PET in assessing therapy response in osseous and soft tissue sarcomas (OSTS) is presented. Methods: This is a retrospective study (January 1999 to December 2004) of 14 patients with histologic diagnosis of OSTS, who had 2 consecutive PET examinations for evaluation of chemotherapy response. The group included 8 men and 6 women, with age range of 18 to 56 years (average, 36 ± 14). Semiquantitative assessment of FDG uptake was performed by calculating maximum standard uptake value (SUVmax) before and after treatment. The response to therapy was assessed independently by tumor necrosis at post-therapy surgery and according to European Organization for Research and Treatment of Cancer (EORTC) criteria for PET. The follow-up PET examinations were performed at an interval of 28 to 166 days (average, 90 ± 45). All patients ended the ifosfamide regimen at 7 to 36 (average, 16 ± 9) days before the follow-up PET scans. Five of them received methotrexate, adriamycin, and/or cisplatin as well. Results: Based on the EORTC criteria alone, 3 patients (21.4%) had progression of disease (increase in SUVmax of 29%–69%; mean, 48% ± 20%), 5 patients (35.7%) had stable disease, and 6 patients (42.8%) had partial response (decrease in SUVmax of 27%–84%; mean, 62% ± 23%). Across all patients, the tumor necrosis postchemotherapy ranged from 5% to 100% (mean, 64% ± 34%). In 8 patients (57.1%) the tumor necrosis correlated with the SUVmax changes. However, for 3 patients, the SUVmax changes indicated partial response despite necrosis of fewer than 90% of the surgical specimens, whereas 3 patients with >90% tumor necrosis had SUVmax changes indicative of stable disease. Conclusion: The pathologically determined degree of necrosis postneoadjuvant chemotherapy was concordant with PET-assessed EORTC classification of response in 57.1% of the cases. However, a significant number of patients had discrepancies, which may be in part explained by chemotherapy-induced inflammation. The latter should be considered during post-therapy PET interpretation in OSTS.

Tumor necrosis has no prognostic value in neoadjuvant chemotherapy for soft tissue sarcoma

Neoadjuvant chemotherapy for treatment of soft tissue sarcomas is controversial, and the correlation between local recurrence and survival is unclear. Histologic necrosis is a well-documented predictor of survival in patients with malignant bone tumors; however, the association is unknown in patients with soft tissue sarcomas. We assessed the prognostic significance of tumor necrosis for treatment of soft tissue sarcomas. We retrospectively collected data from 82 patients who received neoadjuvant chemotherapy for treatment of soft tissue sarcomas of the extremities. Patients had wide resections if tumors were high-grade, deep to the investing fascia, and had clear margins. We quantified the amount of necrosis and analyzed the relationship with local recurrence and overall survival. At an average followup of 65 months (range, 24-154 months), the 5-year local recurrence rates for patients with less than 95% and 95% or greater necrosis were 20% and 33%, respectively. The overall 5-year survivorship rates for patients with less than 95% necrosis and 95% or greater necrosis were 82% and 78%, respectively. There was no difference in recurrencefree survival or overall patient survival based on the amount of histologic necrosis. Tissue necrosis from neoadjuvant chemotherapy does not seem to predict outcome in soft tissue sarcomas.Level of Evidence: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

Serial thallium-201 scintigraphy in osteosarcoma. Correlation with tumor necrosis after preoperative chemotherapy.

In 27 patients with extremity lesions (24 osteosarcoma, three malignant fibrous histiocytoma), a notable decrease in thallium-201 uptake was correlated with a good response to preoperative chemotherapy of the primary tumor. A good response is indicated by a greater than 95% tumor necrosis. Serial quantitative thallium-201 uptake of malignant bone tumors in patients receiving preoperative chemotherapy therefore can accurately predict a good histologic response and prognosis. Serial thallium scintigraphy can furthermore identify poor responses within two weeks after the initiation of treatment, or can prompt an early change in preoperative chemotherapy and facilitate limb salvage surgery.